TY  - JOUR
AU  - Kasalović, Marijana P.
AU  - Dimić, Dušan
AU  - Jelača, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Zmejkovski, Bojana B.
AU  - Schreiner, Simon H. F.
AU  - Rüffer, Tobias
AU  - Pantelić, Nebojša Đ.
AU  - Kaluđerović, Goran N.
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6626
AB  - A novel trimethyltin(IV) complex (Me3SnL), derived from 3-(4-methyl-2-oxoquinolin-1(2H)-yl)propanoate ligand, has been synthesized and characterized by elemental microanalysis, UV/Vis spectrophotometry, FT-IR and multinuclear (1H, 13C and 119Sn) NMR spectroscopies. Furthermore, the structure of the ligand precursor HL was solved using SC-XRD (single-crystal X-ray diffraction). The prediction of UV/Vis and NMR spectra by quantum-chemical methods was performed and compared to experimental findings. The protein binding affinity of Me3SnL towards BSA was determined by spectrofluorometric titration and subsequent molecular docking simulations. Me3SnL has been evaluated for its in vitro anticancer activity against three human cell lines, MCF-7 (breast adenocarcinoma), A375 (melanoma) and HCT116 (colorectal carcinoma), and three mouse tumor cell lines, 4T1 (breast carcinoma), B16 (melanoma) and CT26 (colon carcinoma), using MTT and CV assays. The strong inhibition of A375 cell proliferation, ROS/RNS upregulation and robust lipid peroxidation lead to autophagic cell death upon treatment with Me3SnL.
PB  - Basel: MDPI
T2  - Pharmaceuticals
T1  - Trimethyltin(IV) Bearing 3-(4-Methyl-2-oxoquinolin-1(2H)-yl)propanoate Causes Lipid Peroxidation-Mediated Autophagic Cell Death in Human Melanoma A375 Cells
IS  - 3
VL  - 17
DO  - 10.3390/ph17030372
SP  - 372
ER  - 

@article{
author = "Kasalović, Marijana P. and Dimić, Dušan and Jelača, Sanja and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Zmejkovski, Bojana B. and Schreiner, Simon H. F. and Rüffer, Tobias and Pantelić, Nebojša Đ. and Kaluđerović, Goran N.",
year = "2024",
abstract = "A novel trimethyltin(IV) complex (Me3SnL), derived from 3-(4-methyl-2-oxoquinolin-1(2H)-yl)propanoate ligand, has been synthesized and characterized by elemental microanalysis, UV/Vis spectrophotometry, FT-IR and multinuclear (1H, 13C and 119Sn) NMR spectroscopies. Furthermore, the structure of the ligand precursor HL was solved using SC-XRD (single-crystal X-ray diffraction). The prediction of UV/Vis and NMR spectra by quantum-chemical methods was performed and compared to experimental findings. The protein binding affinity of Me3SnL towards BSA was determined by spectrofluorometric titration and subsequent molecular docking simulations. Me3SnL has been evaluated for its in vitro anticancer activity against three human cell lines, MCF-7 (breast adenocarcinoma), A375 (melanoma) and HCT116 (colorectal carcinoma), and three mouse tumor cell lines, 4T1 (breast carcinoma), B16 (melanoma) and CT26 (colon carcinoma), using MTT and CV assays. The strong inhibition of A375 cell proliferation, ROS/RNS upregulation and robust lipid peroxidation lead to autophagic cell death upon treatment with Me3SnL.",
publisher = "Basel: MDPI",
journal = "Pharmaceuticals",
title = "Trimethyltin(IV) Bearing 3-(4-Methyl-2-oxoquinolin-1(2H)-yl)propanoate Causes Lipid Peroxidation-Mediated Autophagic Cell Death in Human Melanoma A375 Cells",
number = "3",
volume = "17",
doi = "10.3390/ph17030372",
pages = "372"
}

Kasalović, M. P., Dimić, D., Jelača, S., Maksimović-Ivanić, D., Mijatović, S., Zmejkovski, B. B., Schreiner, S. H. F., Rüffer, T., Pantelić, N. Đ.,& Kaluđerović, G. N.. (2024). Trimethyltin(IV) Bearing 3-(4-Methyl-2-oxoquinolin-1(2H)-yl)propanoate Causes Lipid Peroxidation-Mediated Autophagic Cell Death in Human Melanoma A375 Cells. in Pharmaceuticals
Basel: MDPI., 17(3), 372.
https://doi.org/10.3390/ph17030372

Kasalović MP, Dimić D, Jelača S, Maksimović-Ivanić D, Mijatović S, Zmejkovski BB, Schreiner SHF, Rüffer T, Pantelić NĐ, Kaluđerović GN. Trimethyltin(IV) Bearing 3-(4-Methyl-2-oxoquinolin-1(2H)-yl)propanoate Causes Lipid Peroxidation-Mediated Autophagic Cell Death in Human Melanoma A375 Cells. in Pharmaceuticals. 2024;17(3):372.
doi:10.3390/ph17030372 .

Kasalović, Marijana P., Dimić, Dušan, Jelača, Sanja, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Zmejkovski, Bojana B., Schreiner, Simon H. F., Rüffer, Tobias, Pantelić, Nebojša Đ., Kaluđerović, Goran N., "Trimethyltin(IV) Bearing 3-(4-Methyl-2-oxoquinolin-1(2H)-yl)propanoate Causes Lipid Peroxidation-Mediated Autophagic Cell Death in Human Melanoma A375 Cells" in Pharmaceuticals, 17, no. 3 (2024):372,
https://doi.org/10.3390/ph17030372 . .

TY  - JOUR
AU  - Jelača, Sanja
AU  - Jovanović, Ivan
AU  - Bovan, Dijana
AU  - Jovanović, Marina Z.
AU  - Jurišević, Milena M.
AU  - Dunđerović, Duško
AU  - Dajić-Stevanović, Zora
AU  - Arsenijević, Nebojša
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6575
AB  - Ethnomedicinal records have long mentioned the historical usage of Alchemilla vulgaris L. in folk medicine, particularly for the treatment of gynecological issues. Building on this ethnomedicinal knowledge regarding female illnesses, the aim of this research was to evaluate the impact of ethanolic extract of A. vulgaris on mouse breast cancer cells (4T1) in vitro and in vivo, in addition to its effect on the immune compartment in the tumor microenvironment. Behind viability decrease of 4T1 cells induced by treatment with A. vulgaris extract was strong inhibition of cell proliferation accompanied by caspase-dependent apoptosis and autophagic cell death. Observed changes in 4T1 cell culture after treatment were well orchestrated and led to a reduction in metastatic potential through weakened adhesion, invasion, migration, and colony-forming abilities in vitro. Enhanced intracellular production of reactive oxygen and nitrogen species promoted by the treatment might interfere with all the observed effects. Apart from the direct effect on tumor cells, the A. vulgaris extract significantly reduced tumor growth in the solid orthotropic mammary carcinoma model through restitution of efficient local and systemic immune response reflected in enhanced antigen-presenting potential of dendritic cells (DCs) as well as the extent and activity of effector T cells.
PB  - Basel: MDPI
T2  - Pharmaceuticals
T1  - Dual Role of Alchemilla vulgaris L. Extract in Breast Cancer Regression: Reestablishment of Effective Immune Response
IS  - 3
VL  - 17
DO  - 10.3390/ph17030286
SP  - 286
ER  - 

@article{
author = "Jelača, Sanja and Jovanović, Ivan and Bovan, Dijana and Jovanović, Marina Z. and Jurišević, Milena M. and Dunđerović, Duško and Dajić-Stevanović, Zora and Arsenijević, Nebojša and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2024",
abstract = "Ethnomedicinal records have long mentioned the historical usage of Alchemilla vulgaris L. in folk medicine, particularly for the treatment of gynecological issues. Building on this ethnomedicinal knowledge regarding female illnesses, the aim of this research was to evaluate the impact of ethanolic extract of A. vulgaris on mouse breast cancer cells (4T1) in vitro and in vivo, in addition to its effect on the immune compartment in the tumor microenvironment. Behind viability decrease of 4T1 cells induced by treatment with A. vulgaris extract was strong inhibition of cell proliferation accompanied by caspase-dependent apoptosis and autophagic cell death. Observed changes in 4T1 cell culture after treatment were well orchestrated and led to a reduction in metastatic potential through weakened adhesion, invasion, migration, and colony-forming abilities in vitro. Enhanced intracellular production of reactive oxygen and nitrogen species promoted by the treatment might interfere with all the observed effects. Apart from the direct effect on tumor cells, the A. vulgaris extract significantly reduced tumor growth in the solid orthotropic mammary carcinoma model through restitution of efficient local and systemic immune response reflected in enhanced antigen-presenting potential of dendritic cells (DCs) as well as the extent and activity of effector T cells.",
publisher = "Basel: MDPI",
journal = "Pharmaceuticals",
title = "Dual Role of Alchemilla vulgaris L. Extract in Breast Cancer Regression: Reestablishment of Effective Immune Response",
number = "3",
volume = "17",
doi = "10.3390/ph17030286",
pages = "286"
}

Jelača, S., Jovanović, I., Bovan, D., Jovanović, M. Z., Jurišević, M. M., Dunđerović, D., Dajić-Stevanović, Z., Arsenijević, N., Mijatović, S.,& Maksimović-Ivanić, D.. (2024). Dual Role of Alchemilla vulgaris L. Extract in Breast Cancer Regression: Reestablishment of Effective Immune Response. in Pharmaceuticals
Basel: MDPI., 17(3), 286.
https://doi.org/10.3390/ph17030286

Jelača S, Jovanović I, Bovan D, Jovanović MZ, Jurišević MM, Dunđerović D, Dajić-Stevanović Z, Arsenijević N, Mijatović S, Maksimović-Ivanić D. Dual Role of Alchemilla vulgaris L. Extract in Breast Cancer Regression: Reestablishment of Effective Immune Response. in Pharmaceuticals. 2024;17(3):286.
doi:10.3390/ph17030286 .

Jelača, Sanja, Jovanović, Ivan, Bovan, Dijana, Jovanović, Marina Z., Jurišević, Milena M., Dunđerović, Duško, Dajić-Stevanović, Zora, Arsenijević, Nebojša, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Dual Role of Alchemilla vulgaris L. Extract in Breast Cancer Regression: Reestablishment of Effective Immune Response" in Pharmaceuticals, 17, no. 3 (2024):286,
https://doi.org/10.3390/ph17030286 . .

TY  - JOUR
AU  - Kasalović, Marijana P.
AU  - Jelača, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Lađarević, Jelena
AU  - Radovanović, Lidija
AU  - Božić, Bojan
AU  - Mijatović, Sanja
AU  - Pantelić, Nebojša Đ.
AU  - Kaluđerović, Goran N.
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6268
AB  - Three new diphenyltin(IV) complexes, bis(3-(4-methyl-2-oxoquinolinyl-1(2H)-yl)propanoato)diphenyltin(IV) (1), bis(2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato)diphenyltin(IV) (2), and bis(2-(4-hydroxy-2-oxoquinolin-1(2H)-yl)ethanoato)diphenyltin(IV) (3), were synthesized and characterized by elemental microanalysis, FT-IR spectroscopy, and multinuclear (1H, 13C and 119Sn) NMR spectroscopy. Crystal structure of ligand precursor, 3-(4-methyl-2-oxoquinolinyl-1(2H)-yl)propanoic acid (HL1), has been determined by X-ray diffraction studies. Asymmetric bidentate coordination of the carboxylato ligands and skew trapezoidal structures are assumed for the synthesized complexes. In vitro anticancer activity of the synthesized diphenyltin(IV) complexes was evaluated against three human: MCF-7 (breast adenocarcinoma), A375 (melanoma), HCT116 (colorectal carcinoma), and three mouse tumor cell lines: 4 T1 (breast carcinoma), B16 (melanoma), CT26 (colon carcinoma) using MTT and CV assays. The IC50 values fall in the range from 0.1 to 3.7 μM. Flow cytometric analysis and fluorescent microscopy suggest that complex 1 induces caspase-dependent apoptosis followed with strong blockade of cell division in HCT116 cells. Since complex 1 showed ROS/RNS scavenging potential mentioned cytotoxicity was not connected with oxidative stress.
PB  - Elsevier
T2  - Journal of Inorganic Biochemistry
T1  - Novel diphenyltin(IV) complexes with carboxylato N-functionalized 2- quinolone ligands: Synthesis, characterization and in vitro anticancer studies
VL  - 250
DO  - 10.1016/j.jinorgbio.2023.112399
SP  - 112399
ER  - 

@article{
author = "Kasalović, Marijana P. and Jelača, Sanja and Maksimović-Ivanić, Danijela and Lađarević, Jelena and Radovanović, Lidija and Božić, Bojan and Mijatović, Sanja and Pantelić, Nebojša Đ. and Kaluđerović, Goran N.",
year = "2024",
abstract = "Three new diphenyltin(IV) complexes, bis(3-(4-methyl-2-oxoquinolinyl-1(2H)-yl)propanoato)diphenyltin(IV) (1), bis(2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato)diphenyltin(IV) (2), and bis(2-(4-hydroxy-2-oxoquinolin-1(2H)-yl)ethanoato)diphenyltin(IV) (3), were synthesized and characterized by elemental microanalysis, FT-IR spectroscopy, and multinuclear (1H, 13C and 119Sn) NMR spectroscopy. Crystal structure of ligand precursor, 3-(4-methyl-2-oxoquinolinyl-1(2H)-yl)propanoic acid (HL1), has been determined by X-ray diffraction studies. Asymmetric bidentate coordination of the carboxylato ligands and skew trapezoidal structures are assumed for the synthesized complexes. In vitro anticancer activity of the synthesized diphenyltin(IV) complexes was evaluated against three human: MCF-7 (breast adenocarcinoma), A375 (melanoma), HCT116 (colorectal carcinoma), and three mouse tumor cell lines: 4 T1 (breast carcinoma), B16 (melanoma), CT26 (colon carcinoma) using MTT and CV assays. The IC50 values fall in the range from 0.1 to 3.7 μM. Flow cytometric analysis and fluorescent microscopy suggest that complex 1 induces caspase-dependent apoptosis followed with strong blockade of cell division in HCT116 cells. Since complex 1 showed ROS/RNS scavenging potential mentioned cytotoxicity was not connected with oxidative stress.",
publisher = "Elsevier",
journal = "Journal of Inorganic Biochemistry",
title = "Novel diphenyltin(IV) complexes with carboxylato N-functionalized 2- quinolone ligands: Synthesis, characterization and in vitro anticancer studies",
volume = "250",
doi = "10.1016/j.jinorgbio.2023.112399",
pages = "112399"
}

Kasalović, M. P., Jelača, S., Maksimović-Ivanić, D., Lađarević, J., Radovanović, L., Božić, B., Mijatović, S., Pantelić, N. Đ.,& Kaluđerović, G. N.. (2024). Novel diphenyltin(IV) complexes with carboxylato N-functionalized 2- quinolone ligands: Synthesis, characterization and in vitro anticancer studies. in Journal of Inorganic Biochemistry
Elsevier., 250, 112399.
https://doi.org/10.1016/j.jinorgbio.2023.112399

Kasalović MP, Jelača S, Maksimović-Ivanić D, Lađarević J, Radovanović L, Božić B, Mijatović S, Pantelić NĐ, Kaluđerović GN. Novel diphenyltin(IV) complexes with carboxylato N-functionalized 2- quinolone ligands: Synthesis, characterization and in vitro anticancer studies. in Journal of Inorganic Biochemistry. 2024;250:112399.
doi:10.1016/j.jinorgbio.2023.112399 .

Kasalović, Marijana P., Jelača, Sanja, Maksimović-Ivanić, Danijela, Lađarević, Jelena, Radovanović, Lidija, Božić, Bojan, Mijatović, Sanja, Pantelić, Nebojša Đ., Kaluđerović, Goran N., "Novel diphenyltin(IV) complexes with carboxylato N-functionalized 2- quinolone ligands: Synthesis, characterization and in vitro anticancer studies" in Journal of Inorganic Biochemistry, 250 (2024):112399,
https://doi.org/10.1016/j.jinorgbio.2023.112399 . .

TY  - JOUR
AU  - Kazimir, Aleksandr
AU  - Schwarze, Benedikt
AU  - Lönnecke, Peter
AU  - Jelača, Sanja
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6266
AB  - For decades, tamoxifen-based hormone therapy has effectively addressed oestrogen receptor positive (ER+) luminal A breast cancer. Nonetheless, the emergence of tamoxifen resistance required innovative
approaches, leading to hybrid metallodrugs with several therapeutic effects besides the inhibition of oestrogen receptor α (ERα). Drawing inspiration from tamoxifen metabolite structures (4-hydroxytamoxifen
and 4,4′-dihyroxytamoxifen), a phenyl ring was replaced by a bidentate 2,2′-bipyridine donor moiety to give
4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2′-bipyridine (L), enabling coordination of bioactive transition
metal compounds such as copper(II) dichloride, yielding [CuCl(μ-Cl)(L-κ2N,N′)]2 (1). Notably, copper(II)
complex 1 exhibited remarkable activity within the low micromolar concentration range against ER+ human glioblastoma U251, as well as breast carcinomas MDA-MB-361 and MCF-7, surpassing the efficacy of previously reported palladium(II) and platinum(II) dichloride analogs against these cell lines. The pronounced efficacy of complex 1 against triple-negative MDA-MB-231 cells highlights its potential multitherapeutic approach, evident through induction of apoptosis and antioxidant activity. This study evaluates the potential of copper–tamoxifen hybrid complex 1 as a potent therapeutic candidate, highlighting its diverse mechanism of action against challenging breast cancer subtypes.
PB  - Royal Society of Chemistry
T2  - RSC Medicinal Chemistry
T1  - Exploring the potential of tamoxifen-based copper(II) dichloride in breast cancer therapy
DO  - 10.1039/d3md00344b
ER  - 

@article{
author = "Kazimir, Aleksandr and Schwarze, Benedikt and Lönnecke, Peter and Jelača, Sanja and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "For decades, tamoxifen-based hormone therapy has effectively addressed oestrogen receptor positive (ER+) luminal A breast cancer. Nonetheless, the emergence of tamoxifen resistance required innovative
approaches, leading to hybrid metallodrugs with several therapeutic effects besides the inhibition of oestrogen receptor α (ERα). Drawing inspiration from tamoxifen metabolite structures (4-hydroxytamoxifen
and 4,4′-dihyroxytamoxifen), a phenyl ring was replaced by a bidentate 2,2′-bipyridine donor moiety to give
4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2′-bipyridine (L), enabling coordination of bioactive transition
metal compounds such as copper(II) dichloride, yielding [CuCl(μ-Cl)(L-κ2N,N′)]2 (1). Notably, copper(II)
complex 1 exhibited remarkable activity within the low micromolar concentration range against ER+ human glioblastoma U251, as well as breast carcinomas MDA-MB-361 and MCF-7, surpassing the efficacy of previously reported palladium(II) and platinum(II) dichloride analogs against these cell lines. The pronounced efficacy of complex 1 against triple-negative MDA-MB-231 cells highlights its potential multitherapeutic approach, evident through induction of apoptosis and antioxidant activity. This study evaluates the potential of copper–tamoxifen hybrid complex 1 as a potent therapeutic candidate, highlighting its diverse mechanism of action against challenging breast cancer subtypes.",
publisher = "Royal Society of Chemistry",
journal = "RSC Medicinal Chemistry",
title = "Exploring the potential of tamoxifen-based copper(II) dichloride in breast cancer therapy",
doi = "10.1039/d3md00344b"
}

Kazimir, A., Schwarze, B., Lönnecke, P., Jelača, S., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2023). Exploring the potential of tamoxifen-based copper(II) dichloride in breast cancer therapy. in RSC Medicinal Chemistry
Royal Society of Chemistry..
https://doi.org/10.1039/d3md00344b

Kazimir A, Schwarze B, Lönnecke P, Jelača S, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Exploring the potential of tamoxifen-based copper(II) dichloride in breast cancer therapy. in RSC Medicinal Chemistry. 2023;.
doi:10.1039/d3md00344b .

Kazimir, Aleksandr, Schwarze, Benedikt, Lönnecke, Peter, Jelača, Sanja, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Exploring the potential of tamoxifen-based copper(II) dichloride in breast cancer therapy" in RSC Medicinal Chemistry (2023),
https://doi.org/10.1039/d3md00344b . .

TY  - CONF
AU  - Murganić, Blagoje
AU  - Kazimir, Aleksandr
AU  - Jelača, Sanja
AU  - Tanić, Nikola
AU  - Tanić, Nasta
AU  - Hey-Hawkins, Evamarie
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6261
AB  - Рак дојке је најчешћи облик рака код жена са приближно 70% случајева који су
позитивни на хормонске рецепторе (HR+). Прекомерна експресија естрогенског
рецептора (ER) је уско повезана са пролиферацијом тумора. Антиестрогенске те-
рапије, нпр. са тамоксифеном, су уобичајени и ефикасни приступи у лечењу ЕR+
рака дојке. Иако терапија тамоксифеном спада у групу циљаних терапија, његова
ефикасност је доказана и код хормон-независних типова карцинома дојке, што
указује на присуство других интрацелуларних циљних молекула. Иако је тамок-
сифен показао значајну ефикасност у лечењу ER-позитивних карцинома дојке,
бројни пацијенти су развили резистенцију. У циљу повећања његовог потенци-
јала и превазилажења резистенције, тамоксифен је модификован металима као
што су платина (Pt) и паладијум (Pd). Једињења заснована на Pt традиционално
се користе у хемиотерапији, док комплекси Pd могу смањити токсичност и бити
ефикаснији против одређених врста рака. Циљ ове студије био је да се процени
ефикасност тамоксифена модификованог са Pt и Pd на панелу ћелијских линија
рака дојке са различитим статусом експресије рецептора. Дериват тамоксифена
који се користи као лиганд, смањио је вијабилност туморских ћелија независно
од експресије ER, што указује да се његово антитуморско дејство може превас-
ходно приписати ER-независном деловању. Експериментални лекови су изазвали
апоптозу независну од каспаза, са израженијим ефектом у случају деривата на
бази Pd. Ефикасност деривата Pd може се додатно повећати укидањем процеса
аутофагије. Узето заједно, дериватизација тамоксифена је обећавајућа стратегија
у дизајну хибридних молекула.
AB  - Breast cancer is the most prevalent form of cancer in women, with approximately
70% of cases being hormone receptor positive (HR+). While overexpression of estrogen
receptor (ER) is closely related with tumor proliferation, anti-estrogen therapies,
e.g., with tamoxifen, are common and effective approaches. Although treatment with
tamoxifen belongs to the group of targeted therapies, its effectiveness has also been
proven in hormone-independent types of breast cancer, which indicates the presence
of intracellular off-targets. Apart of the fact that tamoxifen showed significant
efficiency in the treatment of ER+ breast cancers, numerous patients developed resistance
towards it. With an aim to amplify its potential and overcome resistance, tamoxifen
has been modified with transition metals such as platinum (Pt) and palladium
(Pd). Pt-based compounds have traditionally been used in cancer chemotherapy,
while Pd complexes may lower the toxicity and be more effective against certain types
of cancer. The aim of this study was to evaluate the efficacy of tamoxifen modified
with Pt and Pd on a panel of breast cancer cell lines with different receptor expression
status. The tamoxifen derivative used as ligand diminished the viability of tumor cells
independently of ER expression, indicating that its antitumor action can be dominantly
ascribed to a ER-independent action. The experimental drugs induced caspase
independent apoptosis, with a more pronounced effect in the case of the Pd-based
derivatives. The efficacy of the Pd derivate can be further increased by abolishment
of the autophagic process. Taken together, derivatization of tamoxifen is a promising
strategy for hybrid molecule design.
PB  - Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
T1  - Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке
T1  - Tamoxifen as a vector for platinum(II) and palladium(II) complexes in breast cancer treatment
SP  - 18
EP  - 19
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6261
ER  - 

@conference{
author = "Murganić, Blagoje and Kazimir, Aleksandr and Jelača, Sanja and Tanić, Nikola and Tanić, Nasta and Hey-Hawkins, Evamarie and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Рак дојке је најчешћи облик рака код жена са приближно 70% случајева који су
позитивни на хормонске рецепторе (HR+). Прекомерна експресија естрогенског
рецептора (ER) је уско повезана са пролиферацијом тумора. Антиестрогенске те-
рапије, нпр. са тамоксифеном, су уобичајени и ефикасни приступи у лечењу ЕR+
рака дојке. Иако терапија тамоксифеном спада у групу циљаних терапија, његова
ефикасност је доказана и код хормон-независних типова карцинома дојке, што
указује на присуство других интрацелуларних циљних молекула. Иако је тамок-
сифен показао значајну ефикасност у лечењу ER-позитивних карцинома дојке,
бројни пацијенти су развили резистенцију. У циљу повећања његовог потенци-
јала и превазилажења резистенције, тамоксифен је модификован металима као
што су платина (Pt) и паладијум (Pd). Једињења заснована на Pt традиционално
се користе у хемиотерапији, док комплекси Pd могу смањити токсичност и бити
ефикаснији против одређених врста рака. Циљ ове студије био је да се процени
ефикасност тамоксифена модификованог са Pt и Pd на панелу ћелијских линија
рака дојке са различитим статусом експресије рецептора. Дериват тамоксифена
који се користи као лиганд, смањио је вијабилност туморских ћелија независно
од експресије ER, што указује да се његово антитуморско дејство може превас-
ходно приписати ER-независном деловању. Експериментални лекови су изазвали
апоптозу независну од каспаза, са израженијим ефектом у случају деривата на
бази Pd. Ефикасност деривата Pd може се додатно повећати укидањем процеса
аутофагије. Узето заједно, дериватизација тамоксифена је обећавајућа стратегија
у дизајну хибридних молекула., Breast cancer is the most prevalent form of cancer in women, with approximately
70% of cases being hormone receptor positive (HR+). While overexpression of estrogen
receptor (ER) is closely related with tumor proliferation, anti-estrogen therapies,
e.g., with tamoxifen, are common and effective approaches. Although treatment with
tamoxifen belongs to the group of targeted therapies, its effectiveness has also been
proven in hormone-independent types of breast cancer, which indicates the presence
of intracellular off-targets. Apart of the fact that tamoxifen showed significant
efficiency in the treatment of ER+ breast cancers, numerous patients developed resistance
towards it. With an aim to amplify its potential and overcome resistance, tamoxifen
has been modified with transition metals such as platinum (Pt) and palladium
(Pd). Pt-based compounds have traditionally been used in cancer chemotherapy,
while Pd complexes may lower the toxicity and be more effective against certain types
of cancer. The aim of this study was to evaluate the efficacy of tamoxifen modified
with Pt and Pd on a panel of breast cancer cell lines with different receptor expression
status. The tamoxifen derivative used as ligand diminished the viability of tumor cells
independently of ER expression, indicating that its antitumor action can be dominantly
ascribed to a ER-independent action. The experimental drugs induced caspase
independent apoptosis, with a more pronounced effect in the case of the Pd-based
derivatives. The efficacy of the Pd derivate can be further increased by abolishment
of the autophagic process. Taken together, derivatization of tamoxifen is a promising
strategy for hybrid molecule design.",
publisher = "Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina",
title = "Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке, Tamoxifen as a vector for platinum(II) and palladium(II) complexes in breast cancer treatment",
pages = "18-19",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6261"
}

Murganić, B., Kazimir, A., Jelača, S., Tanić, N., Tanić, N., Hey-Hawkins, E., Mijatović, S.,& Maksimović-Ivanić, D.. (2023). Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 18-19.
https://hdl.handle.net/21.15107/rcub_ibiss_6261

Murganić B, Kazimir A, Jelača S, Tanić N, Tanić N, Hey-Hawkins E, Mijatović S, Maksimović-Ivanić D. Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina. 2023;:18-19.
https://hdl.handle.net/21.15107/rcub_ibiss_6261 .

Murganić, Blagoje, Kazimir, Aleksandr, Jelača, Sanja, Tanić, Nikola, Tanić, Nasta, Hey-Hawkins, Evamarie, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Tамоксифен као вектор за платинске(II) и паладијумске(II) комплексе у третману рака дојке" in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina (2023):18-19,
https://hdl.handle.net/21.15107/rcub_ibiss_6261 .

TY  - CONF
AU  - Jelača, Sanja
AU  - Braun, Sebastian
AU  - Mijatović, Sanja
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6260
AB  - Tаргетовање медијатора инфламације као што су циклооксигеназа-2 (COX) и 5-липоксигеназа (5-LO) може бити обећавајућа стратегија у лечењу канцера. У циљу побољшања селективности, карборан је уграђен у комерцијалне двоструке инхибиторе COX-2/5-LО. У овој студији, процењена је антитуморска активност деривата di-tert-бутилфенола (R-830, KME-4, E-5110, and S-2474) и њихових одговарајућих аналога карборана (R-830-Cb, KME-4-Cb, E-5110-Cb, S-2474-Cb) на панелу хуманих ћелијских линија рака (A375, A549, HCT116, HT-29, and MDA-MB-231). Третман дериватима
di-tert-бутилфенола смањио је вијабилност свих ћелија рака на дозно зависан начин након 72 h. Истовремено, уградња p-карборан групе је резултирала смањењем цитотоксичног потенцијала за све тестиране аналоге карборана, осим R-830-Cb. Стога су за даље испитивање потенцијалног механизма деловања одабрани R-830 и његов карборан аналог R-830-Cb. За разлику од R-830, његов карборански пандан није утицао на вијабилитет ћелија примарног перитонеалног ексудата, што указује да је уградња карборана побољшала селективност према малигном фенотипу. Смањење вијабилности туморских ћелија изазвано R-830-Cb је праћено губитком дeoбног потенцијала, док је одређени проценат HCT116 ћелија био подвргнут програмираној ћелијској
смрти зависном од каспаза. Паралелно, флуоресцентна микроскопија је открила присуство бројних ћелија са абнормалним нуклеусима и кондензованим хроматином. Даље, обустављање аутофагије употребом инхибитора аутофагије 3-метил аденина (3-МА) и хлорокина, открило је цитопротективну улогу овог процеса, компромитујући активност лека. Сви уочени ефекти били су праћени смањеном производњом реактивних врста кисеоника и азота (ROS/RNS) што указује на поремећен редокс
статус ћелија као одговор на третман. Узевши заједно, аналог R-830-Cb на бази карборана је обећавајући кандидат за даљу процену антитуморског ефекта in vivo.
AB  - Targeting inflammatory mediators, such as cyclooxygenase-2 (COX) and 5-lipoxygenase
(5-LO), may be a promising strategy for the treatment of cancer. To improve the selectivity,
a carborane moiety was incorporated into known dual COX-2/5-LO inhibitors. In the
present study, we have evaluated the antitumor activity of di-tert-butylphenol derivatives
(R-830, KME-4, E-5110, and S-2474) and their respective p-carborane analogs (R-830-Cb,
KME-4-Cb, E-5110-Cb, and S-2474-Cb) on a panel of human cancer cell lines (A375, A549,
HCT116, HT-29, and MDA-MB-231). Treatment with di-tert-butylphenol derivatives decreased
the viability of all cancer cells in a dose-dependent manner after 72 h. At the same
time, incorporation of a p-carborane moiety resulted in diminished cytotoxic potential for
all tested carborane analogs, except R-830-Cb. Thus, for further investigation of the potential
mechanism of action, R-830 and its p-carborane analog R-830-Cb were selected. Differently
to R-830, its carborane counterpart did not affect the viability of primary peritoneal exudate
cells, indicating that incorporation of the carborane cage improved selectivity toward
the malignant phenotype. Tumor cell viability decrease triggered by R-830-Cb was followed
by a loss of dividing potential, while a certain percentage of HCT116 cells was subjected
to caspase-dependent programmed cell death. In parallel, fluorescent microscopy revealed
the presence of numerous cells with abnormally shaped nuclei and condensed chromatin.
Furthermore, abolishment of the autophagy using autophagy inhibitors 3-methyladenine
(3-MA) and chloroquine, revealed a cytoprotective role of this process, compromising the
activity of the drug. All observed effects were accompanied by reduced production of reactive
oxygen and nitrogen species (ROS/RNS) indicating a disturbed redox status of the cells
in response to the treatment. Taken together, carborane-based analog R-830-Cb is a promising
candidate for further assessment of the antitumor effect in vivo.
PB  - Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
T1  - In vitro биолошка евалуација аналога di-tert-бутилфенола на бази p-карборана
T1  - In vitro biological evaluation of p-carborane-based di-tert-butylphenol analogs
SP  - 79
EP  - 80
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6260
ER  - 

@conference{
author = "Jelača, Sanja and Braun, Sebastian and Mijatović, Sanja and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Tаргетовање медијатора инфламације као што су циклооксигеназа-2 (COX) и 5-липоксигеназа (5-LO) може бити обећавајућа стратегија у лечењу канцера. У циљу побољшања селективности, карборан је уграђен у комерцијалне двоструке инхибиторе COX-2/5-LО. У овој студији, процењена је антитуморска активност деривата di-tert-бутилфенола (R-830, KME-4, E-5110, and S-2474) и њихових одговарајућих аналога карборана (R-830-Cb, KME-4-Cb, E-5110-Cb, S-2474-Cb) на панелу хуманих ћелијских линија рака (A375, A549, HCT116, HT-29, and MDA-MB-231). Третман дериватима
di-tert-бутилфенола смањио је вијабилност свих ћелија рака на дозно зависан начин након 72 h. Истовремено, уградња p-карборан групе је резултирала смањењем цитотоксичног потенцијала за све тестиране аналоге карборана, осим R-830-Cb. Стога су за даље испитивање потенцијалног механизма деловања одабрани R-830 и његов карборан аналог R-830-Cb. За разлику од R-830, његов карборански пандан није утицао на вијабилитет ћелија примарног перитонеалног ексудата, што указује да је уградња карборана побољшала селективност према малигном фенотипу. Смањење вијабилности туморских ћелија изазвано R-830-Cb је праћено губитком дeoбног потенцијала, док је одређени проценат HCT116 ћелија био подвргнут програмираној ћелијској
смрти зависном од каспаза. Паралелно, флуоресцентна микроскопија је открила присуство бројних ћелија са абнормалним нуклеусима и кондензованим хроматином. Даље, обустављање аутофагије употребом инхибитора аутофагије 3-метил аденина (3-МА) и хлорокина, открило је цитопротективну улогу овог процеса, компромитујући активност лека. Сви уочени ефекти били су праћени смањеном производњом реактивних врста кисеоника и азота (ROS/RNS) што указује на поремећен редокс
статус ћелија као одговор на третман. Узевши заједно, аналог R-830-Cb на бази карборана је обећавајући кандидат за даљу процену антитуморског ефекта in vivo., Targeting inflammatory mediators, such as cyclooxygenase-2 (COX) and 5-lipoxygenase
(5-LO), may be a promising strategy for the treatment of cancer. To improve the selectivity,
a carborane moiety was incorporated into known dual COX-2/5-LO inhibitors. In the
present study, we have evaluated the antitumor activity of di-tert-butylphenol derivatives
(R-830, KME-4, E-5110, and S-2474) and their respective p-carborane analogs (R-830-Cb,
KME-4-Cb, E-5110-Cb, and S-2474-Cb) on a panel of human cancer cell lines (A375, A549,
HCT116, HT-29, and MDA-MB-231). Treatment with di-tert-butylphenol derivatives decreased
the viability of all cancer cells in a dose-dependent manner after 72 h. At the same
time, incorporation of a p-carborane moiety resulted in diminished cytotoxic potential for
all tested carborane analogs, except R-830-Cb. Thus, for further investigation of the potential
mechanism of action, R-830 and its p-carborane analog R-830-Cb were selected. Differently
to R-830, its carborane counterpart did not affect the viability of primary peritoneal exudate
cells, indicating that incorporation of the carborane cage improved selectivity toward
the malignant phenotype. Tumor cell viability decrease triggered by R-830-Cb was followed
by a loss of dividing potential, while a certain percentage of HCT116 cells was subjected
to caspase-dependent programmed cell death. In parallel, fluorescent microscopy revealed
the presence of numerous cells with abnormally shaped nuclei and condensed chromatin.
Furthermore, abolishment of the autophagy using autophagy inhibitors 3-methyladenine
(3-MA) and chloroquine, revealed a cytoprotective role of this process, compromising the
activity of the drug. All observed effects were accompanied by reduced production of reactive
oxygen and nitrogen species (ROS/RNS) indicating a disturbed redox status of the cells
in response to the treatment. Taken together, carborane-based analog R-830-Cb is a promising
candidate for further assessment of the antitumor effect in vivo.",
publisher = "Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina",
title = "In vitro биолошка евалуација аналога di-tert-бутилфенола на бази p-карборана, In vitro biological evaluation of p-carborane-based di-tert-butylphenol analogs",
pages = "79-80",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6260"
}

Jelača, S., Braun, S., Mijatović, S., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2023). In vitro биолошка евалуација аналога di-tert-бутилфенола на бази p-карборана. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 79-80.
https://hdl.handle.net/21.15107/rcub_ibiss_6260

Jelača S, Braun S, Mijatović S, Hey-Hawkins E, Maksimović-Ivanić D. In vitro биолошка евалуација аналога di-tert-бутилфенола на бази p-карборана. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina. 2023;:79-80.
https://hdl.handle.net/21.15107/rcub_ibiss_6260 .

Jelača, Sanja, Braun, Sebastian, Mijatović, Sanja, Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "In vitro биолошка евалуација аналога di-tert-бутилфенола на бази p-карборана" in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina (2023):79-80,
https://hdl.handle.net/21.15107/rcub_ibiss_6260 .

TY  - CONF
AU  - Jelača, Sanja
AU  - Kasalović, Marijana P.
AU  - Pantelić, Nebojša Đ.
AU  - Kaluđerović, Goran N.
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6239
AB  - Background: The limited efficacy of conventional metal-based chemotherapeutic drugs is attributed to resistance, high toxicity, and numerous side effects, thus providing a platform for design of new metal-based drugs with enhanced properties. Organotin(IV) compounds have already been recognized as promising agents due to their ability to inhibit tumor growth both in in vitro and in vivo. Following this concept, new diphenyltin(IV) complexes incorporating carboxylato N-functionalized 2-quinolones ligands were assessed on different cancer cell lines. Material and Methods: Evaluation of anticancer activity in vitro of the newly synthesized diphenyltin(IV)complexes bis(3-(4-methyl-2-oxoquinolinyl-1(2H)-l)propanoato)diphenyltin(IV), bis(2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato)diphenyltin(IV), and bis(2-(4-hydroxy-2-oxoquinolin-1(2H)-yl)ethanoato)diphenyltin(IV)  (1−3, respectively) as well as ligand precursors (HL1, HL2, and HL3) was determined after 72 h on a panel of cancer cell lines of human and mouse origin (MCF-7, A375, HCT116, 4T1, B16, CT26) using MTT and CV assays. Complex 1 and HCT116 cells were selected for further analysis of the potential mechanism, Flow cytometry for the assessment of cell death, proliferation, caspase activation and production of active oxygen/nitrogen species as well as fluorescent microscopy for detection of nuclei morphology were employed. Results: Obtained results showed a dose-dependent viability decrease in all cell lines exposed to complexes 1−3 with IC50 values in the low micromolar range. Ligand precursors, HL1−HL3 showed no activity up to 200 μM. Complex 1 inhibited cell proliferation and provoked caspase-dependent apoptosis in HCT116 cells. The enhanced presence of autophagosomes determined after the treatment with complex 1 was found to be protective, opposing to apoptosis. The scavenging potential of tested complex 1 on ROS/RNS production can be connected with abolished viability and suppressed proliferation, since HCT116 cells are potent producers of ROS. Conclusions: Taking all together, novel diphenyltin(IV) complexes present promising anticancer agents and should be further tested in vivo.
PB  - Belgrade: Serbian Association for Cancer Research
C3  - Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
T1  - Anticancer activity of diphenyltin(IV) compounds bearing carboxylato N-functionalized 2-quinolones
SP  - 100
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6239
ER  - 

@conference{
author = "Jelača, Sanja and Kasalović, Marijana P. and Pantelić, Nebojša Đ. and Kaluđerović, Goran N. and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Background: The limited efficacy of conventional metal-based chemotherapeutic drugs is attributed to resistance, high toxicity, and numerous side effects, thus providing a platform for design of new metal-based drugs with enhanced properties. Organotin(IV) compounds have already been recognized as promising agents due to their ability to inhibit tumor growth both in in vitro and in vivo. Following this concept, new diphenyltin(IV) complexes incorporating carboxylato N-functionalized 2-quinolones ligands were assessed on different cancer cell lines. Material and Methods: Evaluation of anticancer activity in vitro of the newly synthesized diphenyltin(IV)complexes bis(3-(4-methyl-2-oxoquinolinyl-1(2H)-l)propanoato)diphenyltin(IV), bis(2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato)diphenyltin(IV), and bis(2-(4-hydroxy-2-oxoquinolin-1(2H)-yl)ethanoato)diphenyltin(IV)  (1−3, respectively) as well as ligand precursors (HL1, HL2, and HL3) was determined after 72 h on a panel of cancer cell lines of human and mouse origin (MCF-7, A375, HCT116, 4T1, B16, CT26) using MTT and CV assays. Complex 1 and HCT116 cells were selected for further analysis of the potential mechanism, Flow cytometry for the assessment of cell death, proliferation, caspase activation and production of active oxygen/nitrogen species as well as fluorescent microscopy for detection of nuclei morphology were employed. Results: Obtained results showed a dose-dependent viability decrease in all cell lines exposed to complexes 1−3 with IC50 values in the low micromolar range. Ligand precursors, HL1−HL3 showed no activity up to 200 μM. Complex 1 inhibited cell proliferation and provoked caspase-dependent apoptosis in HCT116 cells. The enhanced presence of autophagosomes determined after the treatment with complex 1 was found to be protective, opposing to apoptosis. The scavenging potential of tested complex 1 on ROS/RNS production can be connected with abolished viability and suppressed proliferation, since HCT116 cells are potent producers of ROS. Conclusions: Taking all together, novel diphenyltin(IV) complexes present promising anticancer agents and should be further tested in vivo.",
publisher = "Belgrade: Serbian Association for Cancer Research",
journal = "Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia",
title = "Anticancer activity of diphenyltin(IV) compounds bearing carboxylato N-functionalized 2-quinolones",
pages = "100",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6239"
}

Jelača, S., Kasalović, M. P., Pantelić, N. Đ., Kaluđerović, G. N., Mijatović, S.,& Maksimović-Ivanić, D.. (2023). Anticancer activity of diphenyltin(IV) compounds bearing carboxylato N-functionalized 2-quinolones. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
Belgrade: Serbian Association for Cancer Research., 100.
https://hdl.handle.net/21.15107/rcub_ibiss_6239

Jelača S, Kasalović MP, Pantelić NĐ, Kaluđerović GN, Mijatović S, Maksimović-Ivanić D. Anticancer activity of diphenyltin(IV) compounds bearing carboxylato N-functionalized 2-quinolones. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. 2023;:100.
https://hdl.handle.net/21.15107/rcub_ibiss_6239 .

Jelača, Sanja, Kasalović, Marijana P., Pantelić, Nebojša Đ., Kaluđerović, Goran N., Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Anticancer activity of diphenyltin(IV) compounds bearing carboxylato N-functionalized 2-quinolones" in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia (2023):100,
https://hdl.handle.net/21.15107/rcub_ibiss_6239 .

TY  - CONF
AU  - Murganić, Blagoje
AU  - Kazimir, Aleksandar
AU  - Jelača, Sanja
AU  - Tanić, Nikola
AU  - Tanić, Nasta
AU  - Hey-Hawkins, Evamarie
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6244
AB  - Background: Estrogen receptor-positive (ER+) breast cancer accounts for approximately 70% of all cases and, concordantly, anti-estrogen therapies present a leading therapeutic choice. Interestingly, tamoxifen, which is the most commonly used drug, has also been proven effective in hormone-independent forms of breast cancer, suggesting the existence of intracellular off-targets. Frequent acquisition of therapy resistance presents a platform for the design of tamoxifen derivatives with a 2,2’-bipyridine unit enabling the coordination of transition metal moieties, such as copper(II) dichloride. Copper (Cu) is an essential element involved in the regulation of cellular growth and development. Disruption of its delicate homeostasis results in severe toxicity and hard medical conditions. Increased demand of cancer cells for this micronutrient makes it a valuable candidate for drug design in cancer treatment. The mechanism of action of Cu complexes is typically based on their ability to induce deadly oxidative stress. This study evaluated the efficacy of a copper–tamoxifen hybrid drug on a panel of breast cancer cell lines with varying receptor expression status. Material and Methods: The viability of breast adenocarcinoma cell lines MCF-7, MDA-MB-361, MDA-MB-231, 4T1 and glioma U251 was estimated by MTT and CV assays. Flow cytometric analysis of cells stained with annexin V-FITC/propidium iodide, ApoStat, acridine orange, dihydrorhodamine 123 (DHR),  dihydroethidium (DHE) or 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF) was used to evaluate cell death, caspase activity, autophagy, production of reactive oxygen and nitrogen species (ROS/RNS), respectively. Results: The Cu-tamoxifen hybrid drug displayed substantially higher hormone-receptor (HR) independent cytotoxic activity compared to previously reported metal complexes with a similar tamoxifen vector.  Massive caspase-dependent apoptotic cell death is partially attenuated by an autophagic process that counteracts death signals. In contrast to the platinum analogue, the copper-based tamoxifen derivative reduces ROS/RNS that may be associated with the intracellular accumulation of the reduced form of CuI which is important for cuproptosis. Conclusion: This study demonstrates the potential of the copper–tamoxifen hybrid drug as an intriguing alternative to commonly used platinum complexes in treatment of cancer. Its safety and efficiency will be further estimated in vivo.
PB  - Belgrade: Serbian Association for Cancer Research
C3  - Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
T1  - Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy
SP  - 95
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6244
ER  - 

@conference{
author = "Murganić, Blagoje and Kazimir, Aleksandar and Jelača, Sanja and Tanić, Nikola and Tanić, Nasta and Hey-Hawkins, Evamarie and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Background: Estrogen receptor-positive (ER+) breast cancer accounts for approximately 70% of all cases and, concordantly, anti-estrogen therapies present a leading therapeutic choice. Interestingly, tamoxifen, which is the most commonly used drug, has also been proven effective in hormone-independent forms of breast cancer, suggesting the existence of intracellular off-targets. Frequent acquisition of therapy resistance presents a platform for the design of tamoxifen derivatives with a 2,2’-bipyridine unit enabling the coordination of transition metal moieties, such as copper(II) dichloride. Copper (Cu) is an essential element involved in the regulation of cellular growth and development. Disruption of its delicate homeostasis results in severe toxicity and hard medical conditions. Increased demand of cancer cells for this micronutrient makes it a valuable candidate for drug design in cancer treatment. The mechanism of action of Cu complexes is typically based on their ability to induce deadly oxidative stress. This study evaluated the efficacy of a copper–tamoxifen hybrid drug on a panel of breast cancer cell lines with varying receptor expression status. Material and Methods: The viability of breast adenocarcinoma cell lines MCF-7, MDA-MB-361, MDA-MB-231, 4T1 and glioma U251 was estimated by MTT and CV assays. Flow cytometric analysis of cells stained with annexin V-FITC/propidium iodide, ApoStat, acridine orange, dihydrorhodamine 123 (DHR),  dihydroethidium (DHE) or 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF) was used to evaluate cell death, caspase activity, autophagy, production of reactive oxygen and nitrogen species (ROS/RNS), respectively. Results: The Cu-tamoxifen hybrid drug displayed substantially higher hormone-receptor (HR) independent cytotoxic activity compared to previously reported metal complexes with a similar tamoxifen vector.  Massive caspase-dependent apoptotic cell death is partially attenuated by an autophagic process that counteracts death signals. In contrast to the platinum analogue, the copper-based tamoxifen derivative reduces ROS/RNS that may be associated with the intracellular accumulation of the reduced form of CuI which is important for cuproptosis. Conclusion: This study demonstrates the potential of the copper–tamoxifen hybrid drug as an intriguing alternative to commonly used platinum complexes in treatment of cancer. Its safety and efficiency will be further estimated in vivo.",
publisher = "Belgrade: Serbian Association for Cancer Research",
journal = "Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia",
title = "Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy",
pages = "95",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6244"
}

Murganić, B., Kazimir, A., Jelača, S., Tanić, N., Tanić, N., Hey-Hawkins, E., Mijatović, S.,& Maksimović-Ivanić, D.. (2023). Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
Belgrade: Serbian Association for Cancer Research., 95.
https://hdl.handle.net/21.15107/rcub_ibiss_6244

Murganić B, Kazimir A, Jelača S, Tanić N, Tanić N, Hey-Hawkins E, Mijatović S, Maksimović-Ivanić D. Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. 2023;:95.
https://hdl.handle.net/21.15107/rcub_ibiss_6244 .

Murganić, Blagoje, Kazimir, Aleksandar, Jelača, Sanja, Tanić, Nikola, Tanić, Nasta, Hey-Hawkins, Evamarie, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Potential of Tamoxifen-based Copper(II) Dichloride in Breast Cancer Therapy" in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia (2023):95,
https://hdl.handle.net/21.15107/rcub_ibiss_6244 .

TY  - CONF
AU  - Jelača, Sanja
AU  - Kasalović, Marijana P.
AU  - Pantelić, Nebojša Đ.
AU  - Kaluđerović, Goran N.
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6236
AB  - Cancer is responsible for millions of deaths worldwide each year and, although great
advances have been made in the treatment options, there are still many issues that must be
addressed in order to improve cancer therapy. In the present work, anticancer effect of
three novel Ph3 SnL complexes (L1 –,3-(4-methyl-2-oxoquinolinyl-1(2H)-yl)propanoato;
L2 –,2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato; L3 –,2-(4-hydroxy-2-oxoquinolin-
1(2H)-yl)ethanoato), was evaluated against several cancer cell lines (MCA-7, A375,
HCT116, 4T1, B16 and CT26). The applied treatment decreased cell viability of all cell
lines after 72 h in a dose-dependent manner with IC50 values in the low micromolar range.
Flow cytometric assessment revealed apoptotic cell death in A375 but not B16 culture,
exposed to tested drug. Morphological signs of apoptosis such as shrunk nuclei and
condensed chromatin were further confirmed by fluorescent microscopy. Same treatment
in B16 lead to cell division block coupled with two-fold increase in the amount of melanin
and tyrosinase activity, indicating the differentiation of B16 cells towards melanocytes. In
the background of different response of two melanoma cell lines lies dissimilar redox
response to the treatment. While in A375 cultures, ROS/RNS production is inhibited in
comparison to control, in B16 cells compound Ph3SnL1 provokes ROS/RNS generation.
Finally, when applied in therapeutic regiment, Ph3SnL1 significantly reduced tumor
volume in C57BL/6 mice.
PB  - Belgrade: Faculty of Chemistry
C3  - Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
T1  - Antitumor potential of novel triphenyltin(IV) complexes with carboxylato N-functionalized 2-quinolone ligands
SP  - 95
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6236
ER  - 

@conference{
author = "Jelača, Sanja and Kasalović, Marijana P. and Pantelić, Nebojša Đ. and Kaluđerović, Goran N. and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Cancer is responsible for millions of deaths worldwide each year and, although great
advances have been made in the treatment options, there are still many issues that must be
addressed in order to improve cancer therapy. In the present work, anticancer effect of
three novel Ph3 SnL complexes (L1 –,3-(4-methyl-2-oxoquinolinyl-1(2H)-yl)propanoato;
L2 –,2-(4-methyl-2-oxoquinolin-1(2H)-yl)ethanoato; L3 –,2-(4-hydroxy-2-oxoquinolin-
1(2H)-yl)ethanoato), was evaluated against several cancer cell lines (MCA-7, A375,
HCT116, 4T1, B16 and CT26). The applied treatment decreased cell viability of all cell
lines after 72 h in a dose-dependent manner with IC50 values in the low micromolar range.
Flow cytometric assessment revealed apoptotic cell death in A375 but not B16 culture,
exposed to tested drug. Morphological signs of apoptosis such as shrunk nuclei and
condensed chromatin were further confirmed by fluorescent microscopy. Same treatment
in B16 lead to cell division block coupled with two-fold increase in the amount of melanin
and tyrosinase activity, indicating the differentiation of B16 cells towards melanocytes. In
the background of different response of two melanoma cell lines lies dissimilar redox
response to the treatment. While in A375 cultures, ROS/RNS production is inhibited in
comparison to control, in B16 cells compound Ph3SnL1 provokes ROS/RNS generation.
Finally, when applied in therapeutic regiment, Ph3SnL1 significantly reduced tumor
volume in C57BL/6 mice.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia",
title = "Antitumor potential of novel triphenyltin(IV) complexes with carboxylato N-functionalized 2-quinolone ligands",
pages = "95",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6236"
}

Jelača, S., Kasalović, M. P., Pantelić, N. Đ., Kaluđerović, G. N., Mijatović, S.,& Maksimović-Ivanić, D.. (2023). Antitumor potential of novel triphenyltin(IV) complexes with carboxylato N-functionalized 2-quinolone ligands. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
Belgrade: Faculty of Chemistry., 95.
https://hdl.handle.net/21.15107/rcub_ibiss_6236

Jelača S, Kasalović MP, Pantelić NĐ, Kaluđerović GN, Mijatović S, Maksimović-Ivanić D. Antitumor potential of novel triphenyltin(IV) complexes with carboxylato N-functionalized 2-quinolone ligands. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia. 2023;:95.
https://hdl.handle.net/21.15107/rcub_ibiss_6236 .

Jelača, Sanja, Kasalović, Marijana P., Pantelić, Nebojša Đ., Kaluđerović, Goran N., Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Antitumor potential of novel triphenyltin(IV) complexes with carboxylato N-functionalized 2-quinolone ligands" in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia (2023):95,
https://hdl.handle.net/21.15107/rcub_ibiss_6236 .

TY  - CONF
AU  - Mihajlović, Ekatarina
AU  - Jelača, Sanja
AU  - Biancalana, Lorenzo
AU  - Chiaverini, Lorenzo
AU  - Mijatović, Sanja
AU  - Zacchini, Stefano
AU  - Marchetti, Fabio
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6219
AB  - Лекови на бази метала се деценијама користе у терапији рака. Нажалост, њихова ефикасност је обично праћена значајном токсичношћу и због тога постоји стална потреба за развојем лекова са побољшаним безбедносним профилом. Гвожђе је важан елемент са строго регулисаним метаболизмом и игра кључну улогу у многим физиолошким процесима у организму, попут раста и развоја, што је посебно важно када су у питању ћелије рака. Пошто имају повећане потребе за гвожђем у односу на здраве ћелије, може се очекивати да ћелије рака буду осетљивије на третман једињењима гвожђа од здравих ћелија. У овој студији, испитан је цитотоксични ефекат бинуклеарних једињења гвожђа са изоцијанидним лигандом (Xyl-NC, XylNC+DMAP, Ind-NC) на ћелијама рака хуманог порекла: А2780 рак јајника, MCF-7 рак дојке и HCT116 колоректални карцином in vitro. Третман испитиваним једињењима је смањио вијабилитет свих ћелија рака, док су А2780 одабране за даље истраживање као најосетљивије. Показало се да третман ћелија рака јајника бинуклеарним једињењима гвожђа са изоцијандним лигандима индукује фероптозу, ћелијску смрт изазвану липидном пероксидацијом зависном од гвожђа. Изненађујуће, фероптоза је праћена инхибицијом продукције радикала који узрокују оксидативни и нитрозативни стрес - водоник пероксида и пероксинитрита. Поред тога, показало се да третман свим једињењима узрокује аутофагију ћелија рака јајника. Третман у комбинацији са инхибитором аутофагије 3-метил аденином додатно смањује вијабилитет ћелија, што сугерише да детектована аутофагија има цитопротективну улогу. Такође, третман испитиваним једињењима значајно је инхибирао пролиферацију ћелија рака јајника. Резултати добијени у овој студији указују да би бинуклеарна једињења гвожђа са изоцијанидним лигандима могла постати обећавајући агенси за лечење рака и стога захтевају додатну пажњу и детаљнија биолошка истраживања
AB  - Metal-based drugs have been used as cancer therapeutics for decades. Unfortunately, their efficacy usually comes with significant toxicity and there is a constant need for the development of drugs with improved safety profile. Iron is an important element with tightly regulated metabolism and plays crucial role in many physiological processes in the body, like growth and development, which is particularly important for cancer cells. Since they have increased iron demands compared to healthy cells, it is expected that they could be more susceptible to treatment with iron compounds than healthy cells. In the present study, the cytotoxic effect of diiron compounds with isocyanide ligands (Xyl-NC, XylNC+DMAP, Ind-NC) was investigated on human cancer cell lines: A2780 ovarian cancer, MCF-7 breast cancer, and HCT116 colorectal carcinoma in vitro. Treatment with experimental compounds decreased the viability of all cancer cell lines, while A2780 was selected for further investigation as the most sensitive one. It was shown that treatment of A2780 cells with diiron compounds with isocyanide ligands caused ferroptosis, cell death induced by iron-dependent lipid peroxidation. Surprisingly, ferroptosis was accompanied by the scavenging of radicals causing oxidative and nitrosative stress - hydrogen peroxide and peroxynitrite. Additionally, all 3 compounds induced autophagy in A2780 cells. Co-treatment with the autophagy inhibitor 3-methyl adenine further decreased cell viability, suggesting that detected autophagy had cytoprotective role. Furthermore, treatment with investigated compounds significantly inhibited the proliferation of A2780 cells. Results obtained in this study indicate that diiron compounds with isocyanide ligands could become promising agents for cancer treatment and therefore, require additional attention and further biological assessment.
improved safety profile. Iron is an important element with tightly regulated metabolism and plays crucial
role in many physiological processes in the body, like growth and development, which is particularly
important for cancer cells. Since they have increased iron demands compared to healthy cells, it is expected
that they could be more susceptible to treatment with iron compounds than healthy cells. In the
present study, the cytotoxic effect of diiron compounds with isocyanide ligands (Xyl-NC, XylNC+DMAP,
Ind-NC) was investigated on human cancer cell lines: A2780 ovarian cancer, MCF-7 breast cancer, and
HCT116 colorectal carcinoma in vitro. Treatment with experimental compounds decreased the viability
of all cancer cell lines, while A2780 was selected for further investigation as the most sensitive one. It was
shown that treatment of A2780 cells with diiron compounds with isocyanide ligands caused ferroptosis,
cell death induced by iron-dependent lipid peroxidation. Surprisingly, ferroptosis was accompanied by
the scavenging of radicals causing oxidative and nitrosative stress - hydrogen peroxide and peroxynitrite.
Additionally, all 3 compounds induced autophagy in A2780 cells. Co-treatment with the autophagy
inhibitor 3-methyl adenine further decreased cell viability, suggesting that detected autophagy had cytoprotective role. Furthermore, treatment with investigated compounds significantly inhibited the proliferation of A2780 cells. Results obtained in this study indicate that diiron compounds with isocyanide
ligands could become promising agents for cancer treatment and therefore, require additional attention
and further biological assessment.
PB  - Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
T1  - Aнтитуморски потенцијал бинуклеарних једињења гвожђа са изоцијанидним лигандом
T1  - Antitumor potential of diiron compounds with isocyanide ligands
SP  - 32
EP  - 33
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6219
ER  - 

@conference{
author = "Mihajlović, Ekatarina and Jelača, Sanja and Biancalana, Lorenzo and Chiaverini, Lorenzo and Mijatović, Sanja and Zacchini, Stefano and Marchetti, Fabio and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Лекови на бази метала се деценијама користе у терапији рака. Нажалост, њихова ефикасност је обично праћена значајном токсичношћу и због тога постоји стална потреба за развојем лекова са побољшаним безбедносним профилом. Гвожђе је важан елемент са строго регулисаним метаболизмом и игра кључну улогу у многим физиолошким процесима у организму, попут раста и развоја, што је посебно важно када су у питању ћелије рака. Пошто имају повећане потребе за гвожђем у односу на здраве ћелије, може се очекивати да ћелије рака буду осетљивије на третман једињењима гвожђа од здравих ћелија. У овој студији, испитан је цитотоксични ефекат бинуклеарних једињења гвожђа са изоцијанидним лигандом (Xyl-NC, XylNC+DMAP, Ind-NC) на ћелијама рака хуманог порекла: А2780 рак јајника, MCF-7 рак дојке и HCT116 колоректални карцином in vitro. Третман испитиваним једињењима је смањио вијабилитет свих ћелија рака, док су А2780 одабране за даље истраживање као најосетљивије. Показало се да третман ћелија рака јајника бинуклеарним једињењима гвожђа са изоцијандним лигандима индукује фероптозу, ћелијску смрт изазвану липидном пероксидацијом зависном од гвожђа. Изненађујуће, фероптоза је праћена инхибицијом продукције радикала који узрокују оксидативни и нитрозативни стрес - водоник пероксида и пероксинитрита. Поред тога, показало се да третман свим једињењима узрокује аутофагију ћелија рака јајника. Третман у комбинацији са инхибитором аутофагије 3-метил аденином додатно смањује вијабилитет ћелија, што сугерише да детектована аутофагија има цитопротективну улогу. Такође, третман испитиваним једињењима значајно је инхибирао пролиферацију ћелија рака јајника. Резултати добијени у овој студији указују да би бинуклеарна једињења гвожђа са изоцијанидним лигандима могла постати обећавајући агенси за лечење рака и стога захтевају додатну пажњу и детаљнија биолошка истраживања, Metal-based drugs have been used as cancer therapeutics for decades. Unfortunately, their efficacy usually comes with significant toxicity and there is a constant need for the development of drugs with improved safety profile. Iron is an important element with tightly regulated metabolism and plays crucial role in many physiological processes in the body, like growth and development, which is particularly important for cancer cells. Since they have increased iron demands compared to healthy cells, it is expected that they could be more susceptible to treatment with iron compounds than healthy cells. In the present study, the cytotoxic effect of diiron compounds with isocyanide ligands (Xyl-NC, XylNC+DMAP, Ind-NC) was investigated on human cancer cell lines: A2780 ovarian cancer, MCF-7 breast cancer, and HCT116 colorectal carcinoma in vitro. Treatment with experimental compounds decreased the viability of all cancer cell lines, while A2780 was selected for further investigation as the most sensitive one. It was shown that treatment of A2780 cells with diiron compounds with isocyanide ligands caused ferroptosis, cell death induced by iron-dependent lipid peroxidation. Surprisingly, ferroptosis was accompanied by the scavenging of radicals causing oxidative and nitrosative stress - hydrogen peroxide and peroxynitrite. Additionally, all 3 compounds induced autophagy in A2780 cells. Co-treatment with the autophagy inhibitor 3-methyl adenine further decreased cell viability, suggesting that detected autophagy had cytoprotective role. Furthermore, treatment with investigated compounds significantly inhibited the proliferation of A2780 cells. Results obtained in this study indicate that diiron compounds with isocyanide ligands could become promising agents for cancer treatment and therefore, require additional attention and further biological assessment.
improved safety profile. Iron is an important element with tightly regulated metabolism and plays crucial
role in many physiological processes in the body, like growth and development, which is particularly
important for cancer cells. Since they have increased iron demands compared to healthy cells, it is expected
that they could be more susceptible to treatment with iron compounds than healthy cells. In the
present study, the cytotoxic effect of diiron compounds with isocyanide ligands (Xyl-NC, XylNC+DMAP,
Ind-NC) was investigated on human cancer cell lines: A2780 ovarian cancer, MCF-7 breast cancer, and
HCT116 colorectal carcinoma in vitro. Treatment with experimental compounds decreased the viability
of all cancer cell lines, while A2780 was selected for further investigation as the most sensitive one. It was
shown that treatment of A2780 cells with diiron compounds with isocyanide ligands caused ferroptosis,
cell death induced by iron-dependent lipid peroxidation. Surprisingly, ferroptosis was accompanied by
the scavenging of radicals causing oxidative and nitrosative stress - hydrogen peroxide and peroxynitrite.
Additionally, all 3 compounds induced autophagy in A2780 cells. Co-treatment with the autophagy
inhibitor 3-methyl adenine further decreased cell viability, suggesting that detected autophagy had cytoprotective role. Furthermore, treatment with investigated compounds significantly inhibited the proliferation of A2780 cells. Results obtained in this study indicate that diiron compounds with isocyanide
ligands could become promising agents for cancer treatment and therefore, require additional attention
and further biological assessment.",
publisher = "Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina",
title = "Aнтитуморски потенцијал бинуклеарних једињења гвожђа са изоцијанидним лигандом, Antitumor potential of diiron compounds with isocyanide ligands",
pages = "32-33",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6219"
}

Mihajlović, E., Jelača, S., Biancalana, L., Chiaverini, L., Mijatović, S., Zacchini, S., Marchetti, F.,& Maksimović-Ivanić, D.. (2023). Aнтитуморски потенцијал бинуклеарних једињења гвожђа са изоцијанидним лигандом. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina
Kragujevac: Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 32-33.
https://hdl.handle.net/21.15107/rcub_ibiss_6219

Mihajlović E, Jelača S, Biancalana L, Chiaverini L, Mijatović S, Zacchini S, Marchetti F, Maksimović-Ivanić D. Aнтитуморски потенцијал бинуклеарних једињења гвожђа са изоцијанидним лигандом. in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina. 2023;:32-33.
https://hdl.handle.net/21.15107/rcub_ibiss_6219 .

Mihajlović, Ekatarina, Jelača, Sanja, Biancalana, Lorenzo, Chiaverini, Lorenzo, Mijatović, Sanja, Zacchini, Stefano, Marchetti, Fabio, Maksimović-Ivanić, Danijela, "Aнтитуморски потенцијал бинуклеарних једињења гвожђа са изоцијанидним лигандом" in Abstract Book: The second Serbian Molecular Medicine Congress; 2023 Oct 6-8; Foča, Bosnia and Herzegovina (2023):32-33,
https://hdl.handle.net/21.15107/rcub_ibiss_6219 .

TY  - CONF
AU  - Mihajlović, Ekatarina
AU  - Jelača, Sanja
AU  - Biancalana, Lorenzo
AU  - Chiaverini, Lorenzo
AU  - Mijatović, Sanja
AU  - Zacchini, Stefano
AU  - Marchetti, Fabio
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6218
AB  - Background: Iron is an important trace element with a broad range of functions in diverse physiological processes and tightly regulated metabolism. Over the years, numerous studies have indicated that cancer cells exhibit an iron-seeking phenotype, meaning they have higher demands for iron than healthy cells. This feature may serve as a foundation for a new approach to cancer therapy. In order to develop anticancer drug with improved efficacy, higher selectivity and reduced toxicity, a new organo-diiron complex with a bridging thiocarbyne ligand (FeSDAP) was synthesized. Material and Methods: The cytotoxic effect of FeSDAP was investigated on mouse cancer cell lines (B16-F1 low-invasive melanoma, B16-F10 high-invasive melanoma and 4T1 breast cancer), as well as on mouse embryonic fibroblasts (NIH-3T3). For investigation of its mechanism of action, flow cytometry and light microscopy were used. To investigate how 72h long exposure to DMAP in vitro affect the potential of B16-F1 and B16-F10 cells to form tumor in vivo, respective subcutaneous synegenic models in C57BL/6 mice were used. Results and Conclusions: Treatment with FeSDAP decreased viability of all cells after 72 hours, with significantly less potent effect on embryionic fibroblasts compared to cancer cells, suggesting FeSDAP may possess selectivity towards malignant phenotype. Melanoma cells were almost equally sensitive to the treatment, but more sensitive than breast cancer cells, so both B16-F1 and B16-F10 were selected for further comparative investigation. Treatment with FeSDAP inhibited proliferation of melanoma cells and caused substantial change in their morphology, which was even more pronounced when it comes to B16-F10 cells. After microscopic evaluation, it was shown that melanoma cells went into senescence. Prominent morphological change of B16-F10 cells was caused by transdifferentiation into Schwann Cell-Like Cells. Further investigation of tumorigenic potential of treated melanoma cells in mice showed that the average tumor size in the groups that received treated cells was significantly smaller, suggesting that melanoma cells have persistently reduced potential to form tumor after single in vitro treatment with FeSDAP. Ultimately, these results strongly indicate that investigated diiron thiocarbyne complexes may display a promising antitumor potential that will be investigated in more detail.
PB  - Belgrade, Serbia: Serbian Associaton for Cancer Research
C3  - Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
T1  - The effect of diiron thiocarbyne complex on tumor cells of different grade
SP  - 61
EP  - 62
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6218
ER  - 

@conference{
author = "Mihajlović, Ekatarina and Jelača, Sanja and Biancalana, Lorenzo and Chiaverini, Lorenzo and Mijatović, Sanja and Zacchini, Stefano and Marchetti, Fabio and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Background: Iron is an important trace element with a broad range of functions in diverse physiological processes and tightly regulated metabolism. Over the years, numerous studies have indicated that cancer cells exhibit an iron-seeking phenotype, meaning they have higher demands for iron than healthy cells. This feature may serve as a foundation for a new approach to cancer therapy. In order to develop anticancer drug with improved efficacy, higher selectivity and reduced toxicity, a new organo-diiron complex with a bridging thiocarbyne ligand (FeSDAP) was synthesized. Material and Methods: The cytotoxic effect of FeSDAP was investigated on mouse cancer cell lines (B16-F1 low-invasive melanoma, B16-F10 high-invasive melanoma and 4T1 breast cancer), as well as on mouse embryonic fibroblasts (NIH-3T3). For investigation of its mechanism of action, flow cytometry and light microscopy were used. To investigate how 72h long exposure to DMAP in vitro affect the potential of B16-F1 and B16-F10 cells to form tumor in vivo, respective subcutaneous synegenic models in C57BL/6 mice were used. Results and Conclusions: Treatment with FeSDAP decreased viability of all cells after 72 hours, with significantly less potent effect on embryionic fibroblasts compared to cancer cells, suggesting FeSDAP may possess selectivity towards malignant phenotype. Melanoma cells were almost equally sensitive to the treatment, but more sensitive than breast cancer cells, so both B16-F1 and B16-F10 were selected for further comparative investigation. Treatment with FeSDAP inhibited proliferation of melanoma cells and caused substantial change in their morphology, which was even more pronounced when it comes to B16-F10 cells. After microscopic evaluation, it was shown that melanoma cells went into senescence. Prominent morphological change of B16-F10 cells was caused by transdifferentiation into Schwann Cell-Like Cells. Further investigation of tumorigenic potential of treated melanoma cells in mice showed that the average tumor size in the groups that received treated cells was significantly smaller, suggesting that melanoma cells have persistently reduced potential to form tumor after single in vitro treatment with FeSDAP. Ultimately, these results strongly indicate that investigated diiron thiocarbyne complexes may display a promising antitumor potential that will be investigated in more detail.",
publisher = "Belgrade, Serbia: Serbian Associaton for Cancer Research",
journal = "Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia",
title = "The effect of diiron thiocarbyne complex on tumor cells of different grade",
pages = "61-62",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6218"
}

Mihajlović, E., Jelača, S., Biancalana, L., Chiaverini, L., Mijatović, S., Zacchini, S., Marchetti, F.,& Maksimović-Ivanić, D.. (2023). The effect of diiron thiocarbyne complex on tumor cells of different grade. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia
Belgrade, Serbia: Serbian Associaton for Cancer Research., 61-62.
https://hdl.handle.net/21.15107/rcub_ibiss_6218

Mihajlović E, Jelača S, Biancalana L, Chiaverini L, Mijatović S, Zacchini S, Marchetti F, Maksimović-Ivanić D. The effect of diiron thiocarbyne complex on tumor cells of different grade. in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia. 2023;:61-62.
https://hdl.handle.net/21.15107/rcub_ibiss_6218 .

Mihajlović, Ekatarina, Jelača, Sanja, Biancalana, Lorenzo, Chiaverini, Lorenzo, Mijatović, Sanja, Zacchini, Stefano, Marchetti, Fabio, Maksimović-Ivanić, Danijela, "The effect of diiron thiocarbyne complex on tumor cells of different grade" in Proceedings book of The Sixth Congress of The Serbian Association for Cancer Research with international participation: From Collaboration to Innovation in Cancer Research; 2023 Oct 2-4; Belgrade, Serbia (2023):61-62,
https://hdl.handle.net/21.15107/rcub_ibiss_6218 .

TY  - CONF
AU  - Mihajlović, Ekatarina
AU  - Jelača, Sanja
AU  - Biancalana, Lorenzo
AU  - Chiaverini, Lorenzo
AU  - Dojčinović, Biljana
AU  - Mijatović, Sanja
AU  - Zacchini, Stefano
AU  - Marchetti, Fabio
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6216
AB  - To improve safety and efficacy of conventional chemotherapeutics, it is important to target
cancer cells more selectively. Potential strategies could arise from differences in iron
metabolism between healthy and cancer cells, based on cancer cells high demands for iron.
Their, so-called, “iron addiction” sets a foundation for new therapeutic approach. In this
study, the cytotoxic effect of three diiron carbonyl complexes with a bridging thiocarbyne
ligand was evaluated on different human cancer cell lines (HCT116 colorectal carcinoma,
MCF-7 breast cancer and A2780 ovarian cancer), as well as on human embryonic lung
fibroblasts (MRC-5), which were used for selectivity assessment. The most potent
compound (FETPY) decreased viability of all cancer cell lines in dose-dependent manner,
while A2780 cells emerged as the most sensitive. Therefore, they were selected for further
investigation. On the other hand, the effect of FETPY on lung fibroblasts viability was
remarkably less potent, showing its great selectivity towards malignant phenotype.
Additionally, it was shown that intracellular iron concentration was much higher in A2780
than in MRC-5 cells after treatment with FETPY. Viability decrease of A2780 cells was a
consequence of cell death – ferroptosis, caused by iron-dependent lipid peroxidation and
membrane damage. Oxidative stress that caused ferroptosis evolved from intensive
production of nitric oxide and superoxide anion. Controversially, it was followed with
scavenging of hydrogen peroxide and peroxynitrite. Treatment with FETPY also caused
significant decrease of A2780 cells division rate. Overall, these results indicate that the
considered diiron derivatives show great potential for further investigation in cancer
treatment.
PB  - Belgrade: Faculty of Chemistry
C3  - Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
T1  - Anticancer potential of diiron thiocarbyne complexes
SP  - 68
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6216
ER  - 

@conference{
author = "Mihajlović, Ekatarina and Jelača, Sanja and Biancalana, Lorenzo and Chiaverini, Lorenzo and Dojčinović, Biljana and Mijatović, Sanja and Zacchini, Stefano and Marchetti, Fabio and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "To improve safety and efficacy of conventional chemotherapeutics, it is important to target
cancer cells more selectively. Potential strategies could arise from differences in iron
metabolism between healthy and cancer cells, based on cancer cells high demands for iron.
Their, so-called, “iron addiction” sets a foundation for new therapeutic approach. In this
study, the cytotoxic effect of three diiron carbonyl complexes with a bridging thiocarbyne
ligand was evaluated on different human cancer cell lines (HCT116 colorectal carcinoma,
MCF-7 breast cancer and A2780 ovarian cancer), as well as on human embryonic lung
fibroblasts (MRC-5), which were used for selectivity assessment. The most potent
compound (FETPY) decreased viability of all cancer cell lines in dose-dependent manner,
while A2780 cells emerged as the most sensitive. Therefore, they were selected for further
investigation. On the other hand, the effect of FETPY on lung fibroblasts viability was
remarkably less potent, showing its great selectivity towards malignant phenotype.
Additionally, it was shown that intracellular iron concentration was much higher in A2780
than in MRC-5 cells after treatment with FETPY. Viability decrease of A2780 cells was a
consequence of cell death – ferroptosis, caused by iron-dependent lipid peroxidation and
membrane damage. Oxidative stress that caused ferroptosis evolved from intensive
production of nitric oxide and superoxide anion. Controversially, it was followed with
scavenging of hydrogen peroxide and peroxynitrite. Treatment with FETPY also caused
significant decrease of A2780 cells division rate. Overall, these results indicate that the
considered diiron derivatives show great potential for further investigation in cancer
treatment.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia",
title = "Anticancer potential of diiron thiocarbyne complexes",
pages = "68",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6216"
}

Mihajlović, E., Jelača, S., Biancalana, L., Chiaverini, L., Dojčinović, B., Mijatović, S., Zacchini, S., Marchetti, F.,& Maksimović-Ivanić, D.. (2023). Anticancer potential of diiron thiocarbyne complexes. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
Belgrade: Faculty of Chemistry., 68.
https://hdl.handle.net/21.15107/rcub_ibiss_6216

Mihajlović E, Jelača S, Biancalana L, Chiaverini L, Dojčinović B, Mijatović S, Zacchini S, Marchetti F, Maksimović-Ivanić D. Anticancer potential of diiron thiocarbyne complexes. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia. 2023;:68.
https://hdl.handle.net/21.15107/rcub_ibiss_6216 .

Mihajlović, Ekatarina, Jelača, Sanja, Biancalana, Lorenzo, Chiaverini, Lorenzo, Dojčinović, Biljana, Mijatović, Sanja, Zacchini, Stefano, Marchetti, Fabio, Maksimović-Ivanić, Danijela, "Anticancer potential of diiron thiocarbyne complexes" in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia (2023):68,
https://hdl.handle.net/21.15107/rcub_ibiss_6216 .

TY  - JOUR
AU  - Braun, Sebastian
AU  - Jelača, Sanja
AU  - Laube, Marcus
AU  - George, Sven
AU  - Hofmann, Bettina
AU  - Lönnecke, Peter
AU  - Steinhilber, Dieter
AU  - Pietzsch, Jens
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5823
AB  - Targeting inflammatory mediators and related signaling pathways may offer a rational strategy for the treatment of cancer. The incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes in dual cycloxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids is a promising approach. The di-tert-butylphenol derivatives R-830, S-2474, KME-4, and E-5110 represent potent dual COX-2/5-LO inhibitors. The incorporation of p-carborane and further substitution of the p-position resulted in four carborane-based di-tert-butylphenol analogs that showed no or weak COX inhibition but high 5-LO inhibitory activities in vitro. Cell viability studies on five human cancer cell lines revealed that the p-carborane analogs R-830-Cb, S-2474-Cb, KME-4-Cb, and E-5110-Cb exhibited lower anticancer activity compared to the related di-tert-butylphenols. Interestingly, R-830-Cb did not affect the viability of primary cells and suppressed HCT116 cell proliferation more potently than its carbon-based R-830 counterpart. Considering all the advantages of boron cluster incorporation for enhancement of drug biostability, selectivity, and availability of drugs, R-830-Cb can be tested in further mechanistic and in vivo studies.
PB  - Basel: MDPI
T2  - Molecules
T1  - Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs
IS  - 11
VL  - 28
DO  - 10.3390/molecules28114547
SP  - 4547
ER  - 

@article{
author = "Braun, Sebastian and Jelača, Sanja and Laube, Marcus and George, Sven and Hofmann, Bettina and Lönnecke, Peter and Steinhilber, Dieter and Pietzsch, Jens and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "Targeting inflammatory mediators and related signaling pathways may offer a rational strategy for the treatment of cancer. The incorporation of metabolically stable, sterically demanding, and hydrophobic carboranes in dual cycloxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids is a promising approach. The di-tert-butylphenol derivatives R-830, S-2474, KME-4, and E-5110 represent potent dual COX-2/5-LO inhibitors. The incorporation of p-carborane and further substitution of the p-position resulted in four carborane-based di-tert-butylphenol analogs that showed no or weak COX inhibition but high 5-LO inhibitory activities in vitro. Cell viability studies on five human cancer cell lines revealed that the p-carborane analogs R-830-Cb, S-2474-Cb, KME-4-Cb, and E-5110-Cb exhibited lower anticancer activity compared to the related di-tert-butylphenols. Interestingly, R-830-Cb did not affect the viability of primary cells and suppressed HCT116 cell proliferation more potently than its carbon-based R-830 counterpart. Considering all the advantages of boron cluster incorporation for enhancement of drug biostability, selectivity, and availability of drugs, R-830-Cb can be tested in further mechanistic and in vivo studies.",
publisher = "Basel: MDPI",
journal = "Molecules",
title = "Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs",
number = "11",
volume = "28",
doi = "10.3390/molecules28114547",
pages = "4547"
}

Braun, S., Jelača, S., Laube, M., George, S., Hofmann, B., Lönnecke, P., Steinhilber, D., Pietzsch, J., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2023). Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs. in Molecules
Basel: MDPI., 28(11), 4547.
https://doi.org/10.3390/molecules28114547

Braun S, Jelača S, Laube M, George S, Hofmann B, Lönnecke P, Steinhilber D, Pietzsch J, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs. in Molecules. 2023;28(11):4547.
doi:10.3390/molecules28114547 .

Braun, Sebastian, Jelača, Sanja, Laube, Marcus, George, Sven, Hofmann, Bettina, Lönnecke, Peter, Steinhilber, Dieter, Pietzsch, Jens, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Synthesis and In Vitro Biological Evaluation of p-Carborane-Based Di-tert-butylphenol Analogs" in Molecules, 28, no. 11 (2023):4547,
https://doi.org/10.3390/molecules28114547 . .

TY  - JOUR
AU  - Markelić, Milica
AU  - Mojić, Marija
AU  - Bovan, Dijana
AU  - Jelača, Sanja
AU  - Jović, Zorana
AU  - Purić, Milica
AU  - Koruga, Djuro
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5470
AB  - In our recent study, we showed that in vitro treatment of melanoma cells with hyperpolarized light (HPL) as well as with the second derivative of fullerene, hyper-harmonized hydroxylated fullerene water complex (3HFWC) reduced viability of cells by decreasing their proliferative capacity and inducing senescence and reprogramming towards a normal, melanocytic phenotype. Therefore, we wanted to determine whether these effects persisted in vivo in the syngeneic mouse melanoma model with a combined treatment of HPL irradiation and 3HFWC per os. Our results demonstrated the potent antitumor effects of 3HFWC nanosubstance assisted by HPL irradiation. These effects were primarily driven by the stimulation of melanoma cell growth arrest, the establishment of a senescent phenotype, and melanocytic differentiation on the one hand, and the awakening of the antitumor immune response on the other. In addition, the combined treatment reduced the protumorigenic activity of immune cells by depleting T regulatory cells, myeloid-derived suppressors, and M2 macrophages. The support of the 3HFWC substance by HPL irradiation may be the axis of the new approach design based on tumor cell reprogramming synchronized with the mobilization of the host’s protective immune response.
PB  - Basel: MDPI
T2  - Nanomaterials
T1  - Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo
IS  - 3
VL  - 13
DO  - 10.3390/nano13030372
SP  - 372
ER  - 

@article{
author = "Markelić, Milica and Mojić, Marija and Bovan, Dijana and Jelača, Sanja and Jović, Zorana and Purić, Milica and Koruga, Djuro and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "In our recent study, we showed that in vitro treatment of melanoma cells with hyperpolarized light (HPL) as well as with the second derivative of fullerene, hyper-harmonized hydroxylated fullerene water complex (3HFWC) reduced viability of cells by decreasing their proliferative capacity and inducing senescence and reprogramming towards a normal, melanocytic phenotype. Therefore, we wanted to determine whether these effects persisted in vivo in the syngeneic mouse melanoma model with a combined treatment of HPL irradiation and 3HFWC per os. Our results demonstrated the potent antitumor effects of 3HFWC nanosubstance assisted by HPL irradiation. These effects were primarily driven by the stimulation of melanoma cell growth arrest, the establishment of a senescent phenotype, and melanocytic differentiation on the one hand, and the awakening of the antitumor immune response on the other. In addition, the combined treatment reduced the protumorigenic activity of immune cells by depleting T regulatory cells, myeloid-derived suppressors, and M2 macrophages. The support of the 3HFWC substance by HPL irradiation may be the axis of the new approach design based on tumor cell reprogramming synchronized with the mobilization of the host’s protective immune response.",
publisher = "Basel: MDPI",
journal = "Nanomaterials",
title = "Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo",
number = "3",
volume = "13",
doi = "10.3390/nano13030372",
pages = "372"
}

Markelić, M., Mojić, M., Bovan, D., Jelača, S., Jović, Z., Purić, M., Koruga, D., Mijatović, S.,& Maksimović-Ivanić, D.. (2023). Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo. in Nanomaterials
Basel: MDPI., 13(3), 372.
https://doi.org/10.3390/nano13030372

Markelić M, Mojić M, Bovan D, Jelača S, Jović Z, Purić M, Koruga D, Mijatović S, Maksimović-Ivanić D. Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo. in Nanomaterials. 2023;13(3):372.
doi:10.3390/nano13030372 .

Markelić, Milica, Mojić, Marija, Bovan, Dijana, Jelača, Sanja, Jović, Zorana, Purić, Milica, Koruga, Djuro, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Melanoma Cell Reprogramming and Awakening of Antitumor Immunity as a Fingerprint of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC) and Hyperpolarized Light Application In Vivo" in Nanomaterials, 13, no. 3 (2023):372,
https://doi.org/10.3390/nano13030372 . .

TY  - JOUR
AU  - Kazimir, Aleksandr
AU  - Schwarze, Benedikt
AU  - Lönnecke, Peter
AU  - Jelača, Sanja
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5469
AB  - The luminal A-subtype of breast cancer, where the oestrogen receptor α (ERα) is overexpressed, is the most frequent one. The prodrug tamoxifen (1) is the clinically used agent, inhibiting the ERα activity via the formation of several active metabolites, such as 4-hydroxytamoxifen (2) or 4,4′-dihydroxytamoxifen (3). In this study, we present the tamoxifen derivative 4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2′-bipyridine (4), which was combined with platinum or palladium dichloride, the former a well-known scaffold in anticancer treatment, to give [PtCl2(4-κ2N,N′)] (5) or [PdCl2(4-κ2N,N′] (6). To prevent fast exchange of weakly coordinating chlorido ligands in aqueous solution, a bulky, highly stable and hydrophobic nido-carborate(−2) ([C2B9H11]2−) was incorporated. The resulting complexes [3-(4-κ2N,N′)-3,1,2-PtC2B9H11] (7) and [3-(4-κ2N,N′)-3,1,2-PdC2B9H11] (8) exhibit a dramatic change in electronic and biological properties compared to 5 and 6. Thus, 8 is highly selective for triple-negative MDA-MB-231 cells (IC50 = 3.7 μM, MTT test), while 7 is completely inactive against this cell line. The observed cytotoxicity of compounds 4–6 and 8 against this triple-negative cell line suggests off-target mechanisms rather than only ERα inhibition, for which these compounds were originally designed. Spectroscopic properties and electronic structures of the metal complexes were investigated for possible explanations of the biological activities.
PB  - Basel: MDPI
T2  - Pharmaceutics
T1  - Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes
IS  - 2
VL  - 15
DO  - 10.3390/pharmaceutics15020682
SP  - 682
ER  - 

@article{
author = "Kazimir, Aleksandr and Schwarze, Benedikt and Lönnecke, Peter and Jelača, Sanja and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "The luminal A-subtype of breast cancer, where the oestrogen receptor α (ERα) is overexpressed, is the most frequent one. The prodrug tamoxifen (1) is the clinically used agent, inhibiting the ERα activity via the formation of several active metabolites, such as 4-hydroxytamoxifen (2) or 4,4′-dihydroxytamoxifen (3). In this study, we present the tamoxifen derivative 4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2′-bipyridine (4), which was combined with platinum or palladium dichloride, the former a well-known scaffold in anticancer treatment, to give [PtCl2(4-κ2N,N′)] (5) or [PdCl2(4-κ2N,N′] (6). To prevent fast exchange of weakly coordinating chlorido ligands in aqueous solution, a bulky, highly stable and hydrophobic nido-carborate(−2) ([C2B9H11]2−) was incorporated. The resulting complexes [3-(4-κ2N,N′)-3,1,2-PtC2B9H11] (7) and [3-(4-κ2N,N′)-3,1,2-PdC2B9H11] (8) exhibit a dramatic change in electronic and biological properties compared to 5 and 6. Thus, 8 is highly selective for triple-negative MDA-MB-231 cells (IC50 = 3.7 μM, MTT test), while 7 is completely inactive against this cell line. The observed cytotoxicity of compounds 4–6 and 8 against this triple-negative cell line suggests off-target mechanisms rather than only ERα inhibition, for which these compounds were originally designed. Spectroscopic properties and electronic structures of the metal complexes were investigated for possible explanations of the biological activities.",
publisher = "Basel: MDPI",
journal = "Pharmaceutics",
title = "Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes",
number = "2",
volume = "15",
doi = "10.3390/pharmaceutics15020682",
pages = "682"
}

Kazimir, A., Schwarze, B., Lönnecke, P., Jelača, S., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2023). Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes. in Pharmaceutics
Basel: MDPI., 15(2), 682.
https://doi.org/10.3390/pharmaceutics15020682

Kazimir A, Schwarze B, Lönnecke P, Jelača S, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes. in Pharmaceutics. 2023;15(2):682.
doi:10.3390/pharmaceutics15020682 .

Kazimir, Aleksandr, Schwarze, Benedikt, Lönnecke, Peter, Jelača, Sanja, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Metallodrugs against Breast Cancer: Combining the Tamoxifen Vector with Platinum(II) and Palladium(II) Complexes" in Pharmaceutics, 15, no. 2 (2023):682,
https://doi.org/10.3390/pharmaceutics15020682 . .

TY  - JOUR
AU  - Jelača, Sanja
AU  - Dajić-Stevanović, Zora
AU  - Vuković, Nenad
AU  - Kolašinac, Stefan
AU  - Trendafilova, Antoaneta
AU  - Nedialkov, Paraskev
AU  - Stanković, Miroslava
AU  - Tanić, Nasta
AU  - Tanić, Nikola
AU  - Acović, Aleksandar
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5300
AB  - Alchemilla vulgaris L. (lady’s mantle) was used for centuries in Europe and Balkan countries for treatments of numerous conditions and diseases of the reproductive system, yet some of the biological activities of lady’s mantle have been poorly studied and neglected. The present study aimed to estimate the potential of A. vulgaris ethanolic extract from Southeast Serbia to prevent and suppress tumor development in vitro, validated by antioxidant, genoprotective, and cytotoxic properties. A total of 45 compounds were detected by UHPLC–HRMS analysis in A. vulgaris ethanolic extract. Measurement of antioxidant activity revealed the significant potential of the tested extract to scavenge free radicals. In addition, the analysis of micronuclei showed an in vitro protective effect on chromosome aberrations in peripheral human lymphocytes. A. vulgaris extract strongly suppressed the growth of human cell lines derived from different types of tumors (MCF-7, A375, A549, and HCT116). The observed antitumor effect is realized through the blockade of cell division, caspase-dependent apoptosis, and autophagic cell death. Our study has shown that Alchemilla vulgaris L. is a valuable source of bioactive compounds able to protect the subcellular structure from damage, thus preventing tumorigenesis as well as suppressing tumor cell growth.
PB  - Basel: MDPI
T2  - Molecules
T1  - Beyond Traditional Use of Alchemilla vulgaris: Genoprotective and Antitumor Activity In Vitro
IS  - 23
VL  - 27
DO  - 10.3390/molecules27238113
SP  - 8113
ER  - 

@article{
author = "Jelača, Sanja and Dajić-Stevanović, Zora and Vuković, Nenad and Kolašinac, Stefan and Trendafilova, Antoaneta and Nedialkov, Paraskev and Stanković, Miroslava and Tanić, Nasta and Tanić, Nikola and Acović, Aleksandar and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "Alchemilla vulgaris L. (lady’s mantle) was used for centuries in Europe and Balkan countries for treatments of numerous conditions and diseases of the reproductive system, yet some of the biological activities of lady’s mantle have been poorly studied and neglected. The present study aimed to estimate the potential of A. vulgaris ethanolic extract from Southeast Serbia to prevent and suppress tumor development in vitro, validated by antioxidant, genoprotective, and cytotoxic properties. A total of 45 compounds were detected by UHPLC–HRMS analysis in A. vulgaris ethanolic extract. Measurement of antioxidant activity revealed the significant potential of the tested extract to scavenge free radicals. In addition, the analysis of micronuclei showed an in vitro protective effect on chromosome aberrations in peripheral human lymphocytes. A. vulgaris extract strongly suppressed the growth of human cell lines derived from different types of tumors (MCF-7, A375, A549, and HCT116). The observed antitumor effect is realized through the blockade of cell division, caspase-dependent apoptosis, and autophagic cell death. Our study has shown that Alchemilla vulgaris L. is a valuable source of bioactive compounds able to protect the subcellular structure from damage, thus preventing tumorigenesis as well as suppressing tumor cell growth.",
publisher = "Basel: MDPI",
journal = "Molecules",
title = "Beyond Traditional Use of Alchemilla vulgaris: Genoprotective and Antitumor Activity In Vitro",
number = "23",
volume = "27",
doi = "10.3390/molecules27238113",
pages = "8113"
}

Jelača, S., Dajić-Stevanović, Z., Vuković, N., Kolašinac, S., Trendafilova, A., Nedialkov, P., Stanković, M., Tanić, N., Tanić, N., Acović, A., Mijatović, S.,& Maksimović-Ivanić, D.. (2022). Beyond Traditional Use of Alchemilla vulgaris: Genoprotective and Antitumor Activity In Vitro. in Molecules
Basel: MDPI., 27(23), 8113.
https://doi.org/10.3390/molecules27238113

Jelača S, Dajić-Stevanović Z, Vuković N, Kolašinac S, Trendafilova A, Nedialkov P, Stanković M, Tanić N, Tanić N, Acović A, Mijatović S, Maksimović-Ivanić D. Beyond Traditional Use of Alchemilla vulgaris: Genoprotective and Antitumor Activity In Vitro. in Molecules. 2022;27(23):8113.
doi:10.3390/molecules27238113 .

Jelača, Sanja, Dajić-Stevanović, Zora, Vuković, Nenad, Kolašinac, Stefan, Trendafilova, Antoaneta, Nedialkov, Paraskev, Stanković, Miroslava, Tanić, Nasta, Tanić, Nikola, Acović, Aleksandar, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Beyond Traditional Use of Alchemilla vulgaris: Genoprotective and Antitumor Activity In Vitro" in Molecules, 27, no. 23 (2022):8113,
https://doi.org/10.3390/molecules27238113 . .

TY  - CONF
AU  - Jelača, Sanja
AU  - Drača, Dijana
AU  - Dajić-Stevanović, Zora
AU  - Jovanović, Ivan
AU  - Pavlović, Sladjana
AU  - Gajović, Nevena
AU  - Mijatović, Sanja
AU  - Arsenijević, Nebojša
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5297
AB  - Alchemilla vulgaris is well known for its diverse biological properties such as antiinflammatory,
antioxidant, wound healing, neuroprotective as well as for the treatment of female reproductive
system disorders. Our previous results showed that Alchemilla vulgaris agg. ethanol extract suppresses
the growth of melanoma cells in vitro and in vivo. The aim of this research was to evaluate the effect
of this extract on immune response in spleen and tumor microenvironment in syngeneic model of solid
melanoma. The obtained results strongly suggest that treatment with A. vulgaris extract significantly
modulates the systemic, as well as local intratumor immune response. A similar response was observed
in the spleen and tumor microenvironment. Applied treatment significantly increases the accumulation
of cytotoxic lymphocytes, while reducing the percentage of CD8+ cells that express inhibitory molecules
on their surface. On the other hand, treatment increased expression of cytotoxic activity markers of
CD8+ T cells derived from spleen and primary tumor. In line with this, A. vulgaris extract facilitates
maturation of dendritic cells making them efficient initiators as well as regulators of acquired immune
response to growing tumors. All mentioned above suggest that Alchemilla vulgaris agg. ethanol extract
diminishes immunosuppressive branch of immune response and stimulates the antitumor activities of
immune system through accumulation of cytotoxic lymphocytes and DCs maturation.
PB  - EFIS Young Immunologist Network (yEFIS Network)
C3  - Abstract Book: 1st Symposium: Shaping the Future of Immunology in Europe; 2022 Nov 10-11; Berlin, Germany
T1  - Alchemilla vulgaris agg ethanol extract enhances the antitumor immune response in syngeneic mouse melanoma model
DO  - 10.1002/eji.202270200
SP  - 69
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5297
ER  - 

@conference{
author = "Jelača, Sanja and Drača, Dijana and Dajić-Stevanović, Zora and Jovanović, Ivan and Pavlović, Sladjana and Gajović, Nevena and Mijatović, Sanja and Arsenijević, Nebojša and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "Alchemilla vulgaris is well known for its diverse biological properties such as antiinflammatory,
antioxidant, wound healing, neuroprotective as well as for the treatment of female reproductive
system disorders. Our previous results showed that Alchemilla vulgaris agg. ethanol extract suppresses
the growth of melanoma cells in vitro and in vivo. The aim of this research was to evaluate the effect
of this extract on immune response in spleen and tumor microenvironment in syngeneic model of solid
melanoma. The obtained results strongly suggest that treatment with A. vulgaris extract significantly
modulates the systemic, as well as local intratumor immune response. A similar response was observed
in the spleen and tumor microenvironment. Applied treatment significantly increases the accumulation
of cytotoxic lymphocytes, while reducing the percentage of CD8+ cells that express inhibitory molecules
on their surface. On the other hand, treatment increased expression of cytotoxic activity markers of
CD8+ T cells derived from spleen and primary tumor. In line with this, A. vulgaris extract facilitates
maturation of dendritic cells making them efficient initiators as well as regulators of acquired immune
response to growing tumors. All mentioned above suggest that Alchemilla vulgaris agg. ethanol extract
diminishes immunosuppressive branch of immune response and stimulates the antitumor activities of
immune system through accumulation of cytotoxic lymphocytes and DCs maturation.",
publisher = "EFIS Young Immunologist Network (yEFIS Network)",
journal = "Abstract Book: 1st Symposium: Shaping the Future of Immunology in Europe; 2022 Nov 10-11; Berlin, Germany",
title = "Alchemilla vulgaris agg ethanol extract enhances the antitumor immune response in syngeneic mouse melanoma model",
doi = "10.1002/eji.202270200",
pages = "69",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5297"
}

Jelača, S., Drača, D., Dajić-Stevanović, Z., Jovanović, I., Pavlović, S., Gajović, N., Mijatović, S., Arsenijević, N.,& Maksimović-Ivanić, D.. (2022). Alchemilla vulgaris agg ethanol extract enhances the antitumor immune response in syngeneic mouse melanoma model. in Abstract Book: 1st Symposium: Shaping the Future of Immunology in Europe; 2022 Nov 10-11; Berlin, Germany
EFIS Young Immunologist Network (yEFIS Network)., 69.
https://doi.org/10.1002/eji.202270200
https://hdl.handle.net/21.15107/rcub_ibiss_5297

Jelača S, Drača D, Dajić-Stevanović Z, Jovanović I, Pavlović S, Gajović N, Mijatović S, Arsenijević N, Maksimović-Ivanić D. Alchemilla vulgaris agg ethanol extract enhances the antitumor immune response in syngeneic mouse melanoma model. in Abstract Book: 1st Symposium: Shaping the Future of Immunology in Europe; 2022 Nov 10-11; Berlin, Germany. 2022;:69.
doi:10.1002/eji.202270200
https://hdl.handle.net/21.15107/rcub_ibiss_5297 .

Jelača, Sanja, Drača, Dijana, Dajić-Stevanović, Zora, Jovanović, Ivan, Pavlović, Sladjana, Gajović, Nevena, Mijatović, Sanja, Arsenijević, Nebojša, Maksimović-Ivanić, Danijela, "Alchemilla vulgaris agg ethanol extract enhances the antitumor immune response in syngeneic mouse melanoma model" in Abstract Book: 1st Symposium: Shaping the Future of Immunology in Europe; 2022 Nov 10-11; Berlin, Germany (2022):69,
https://doi.org/10.1002/eji.202270200 .,
https://hdl.handle.net/21.15107/rcub_ibiss_5297 .

TY  - CONF
AU  - Golić, Igor
AU  - Krajnović, Tamara
AU  - Jelača, Sanja
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Koruga, Đuro
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5296
AB  - Fullerene C60 is the third allotropic modification of carbon in nature. Exceptional physical and
structural features of C60 molecule make it attractive for biomedical research in a wide spectrum of
applications from imaging, drug delivery, to therapy of different disorders. However, its low
solubility in water or polar solvents, and genotoxic potential represent serious barriers for its usage.
To overcome mentioned limits the second derivative of fullerene C60 (Hyper harmonized
hydroxylated fullerene water complex - 3HFWC) is created through functionalization of the first
fullerene C60 derivative (fullerol - C60(OH)x) by the addition of paired OH groups in water layers
surrounding the solid phase of substance. The solid phase consists of the C60 molecule, covalent OH
groups and 3-6 water layers with strong hydrogen bonds. The liquid phase consists of additional
water layers bonded by moderate to weak hydrogen bonds. In addition, the third derivative of
fullerene is made when 3HFWC was integrated with nano-gold particles (nAu@3HFWC). The aim
of this study was to evaluate fullerene C60 derivatives uptake and their intracellular distribution in
mouse 3T3 fibroblasts. Cells were exposed to 30 μg/ml C60(OH)x, or 30 μg/ml 3HFWC, or 5μg/ml
nAu@3HFWC during 30 min, 1h or 2h and analysis was done by Philips FEI CM12 transmission
electron microscope. Ultrastructural analysis showed mainly cytoplasmic localization of C60(OH)x
and its derivatives, and also a sporadic presence in mitochondria and nuclei. The concentration of
fullerene derivatives in these cells was time-dependent, i.e., more concentration was observed in
cells with longer exposition to these fullerenes. Furthermore, C60(OH)x is also localized in lysosomes
in higher concentrations. These results suggest that novel C60 fullerene derivatives show better
biocompatibility in mouse 3T3 fibroblasts compared to C60(OH)x, which mainly ends in lysosomes,
the waste disposal system of the cell.
PB  - Belgrade: Serbian Academy of Sciences and Arts
C3  - Program and Book of Abstracts: Second International Conference ELMINA; 2022 Aug 22-26. Belgrade, Serbia
T1  - Investigation of the Action of the Fullerene (C60) Derivatives on Mouse 3T3 Fibroblast Cell Lines
SP  - 84
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5296
ER  - 

@conference{
author = "Golić, Igor and Krajnović, Tamara and Jelača, Sanja and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Koruga, Đuro",
year = "2022",
abstract = "Fullerene C60 is the third allotropic modification of carbon in nature. Exceptional physical and
structural features of C60 molecule make it attractive for biomedical research in a wide spectrum of
applications from imaging, drug delivery, to therapy of different disorders. However, its low
solubility in water or polar solvents, and genotoxic potential represent serious barriers for its usage.
To overcome mentioned limits the second derivative of fullerene C60 (Hyper harmonized
hydroxylated fullerene water complex - 3HFWC) is created through functionalization of the first
fullerene C60 derivative (fullerol - C60(OH)x) by the addition of paired OH groups in water layers
surrounding the solid phase of substance. The solid phase consists of the C60 molecule, covalent OH
groups and 3-6 water layers with strong hydrogen bonds. The liquid phase consists of additional
water layers bonded by moderate to weak hydrogen bonds. In addition, the third derivative of
fullerene is made when 3HFWC was integrated with nano-gold particles (nAu@3HFWC). The aim
of this study was to evaluate fullerene C60 derivatives uptake and their intracellular distribution in
mouse 3T3 fibroblasts. Cells were exposed to 30 μg/ml C60(OH)x, or 30 μg/ml 3HFWC, or 5μg/ml
nAu@3HFWC during 30 min, 1h or 2h and analysis was done by Philips FEI CM12 transmission
electron microscope. Ultrastructural analysis showed mainly cytoplasmic localization of C60(OH)x
and its derivatives, and also a sporadic presence in mitochondria and nuclei. The concentration of
fullerene derivatives in these cells was time-dependent, i.e., more concentration was observed in
cells with longer exposition to these fullerenes. Furthermore, C60(OH)x is also localized in lysosomes
in higher concentrations. These results suggest that novel C60 fullerene derivatives show better
biocompatibility in mouse 3T3 fibroblasts compared to C60(OH)x, which mainly ends in lysosomes,
the waste disposal system of the cell.",
publisher = "Belgrade: Serbian Academy of Sciences and Arts",
journal = "Program and Book of Abstracts: Second International Conference ELMINA; 2022 Aug 22-26. Belgrade, Serbia",
title = "Investigation of the Action of the Fullerene (C60) Derivatives on Mouse 3T3 Fibroblast Cell Lines",
pages = "84",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5296"
}

Golić, I., Krajnović, T., Jelača, S., Mijatović, S., Maksimović-Ivanić, D.,& Koruga, Đ.. (2022). Investigation of the Action of the Fullerene (C60) Derivatives on Mouse 3T3 Fibroblast Cell Lines. in Program and Book of Abstracts: Second International Conference ELMINA; 2022 Aug 22-26. Belgrade, Serbia
Belgrade: Serbian Academy of Sciences and Arts., 84.
https://hdl.handle.net/21.15107/rcub_ibiss_5296

Golić I, Krajnović T, Jelača S, Mijatović S, Maksimović-Ivanić D, Koruga Đ. Investigation of the Action of the Fullerene (C60) Derivatives on Mouse 3T3 Fibroblast Cell Lines. in Program and Book of Abstracts: Second International Conference ELMINA; 2022 Aug 22-26. Belgrade, Serbia. 2022;:84.
https://hdl.handle.net/21.15107/rcub_ibiss_5296 .

Golić, Igor, Krajnović, Tamara, Jelača, Sanja, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Koruga, Đuro, "Investigation of the Action of the Fullerene (C60) Derivatives on Mouse 3T3 Fibroblast Cell Lines" in Program and Book of Abstracts: Second International Conference ELMINA; 2022 Aug 22-26. Belgrade, Serbia (2022):84,
https://hdl.handle.net/21.15107/rcub_ibiss_5296 .

TY  - CONF
AU  - Jelača, Sanja
AU  - Drača, Dijana
AU  - Dajić-Stevanović, Zora
AU  - Jovanović, Ivan
AU  - Tanić, Nikola
AU  - Mijatović, Sanja
AU  - Arsenijević, Nebojša
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5290
AB  - Alchemilla vulgaris is well known in traditional medicine especially for the treatment
of gynecological problems in women. Several ethnomedicinal studies for the territory
of Balkan reports its well known biological properties against many conditions such
as infertility, dysmenorrhea, cysts, menopausal complaints and endometriosis.
Concidering ethnomedicinal data on female illnesses, the aim of our study was to
determine whether ethanol extract of Alchemilla vulgaris agg. exert antitumor effect
against mouse breast cancer cells in vitro. Treatment with Alchemilla vulgaris agg. extract
decreased viability of mouse breast cancer cells (4T1) in dose-dependent manner after
72 h. The viability decrease was followed by loss of dividing potential after the treatment.
In parallel with this, certain percentage of 4T1 cells was subjected to programmed cell
death ̶ apoptosis. Detected apoptosis was followed with caspase activation while typical
apoptotic morphology of treated cells was observed by fluorescent microscopy. Apart
from inhibited cell division and induced apoptosis, decreased cell viability was due to
triggered autophagy cell death. In parallel, diminished metastatic potential of these
cells was confirmed by abrogated adhesion, invasion, migration and decreased colony
forming potential after the treatment. All mentioned effects can be connected with
enhanced production of ROS and intracellular NO after the treatment with Alchemilla
vulgaris agg. Taken together, the effect of Alchemilla vulgaris agg. against breast cancer
cells makes this plant worthwhile for further evaluation in the field of oncology.
AB  - Alchemilla vulgaris је добро позната у традиционалној медицини, посебно за
лечење гинеколошких тегоба код жена. Неколико етномедицинских студија за
територију Балкана описује благотворна дејства ове биљке против различитих
патолошких стања попут неплодности, дисменореје, циста, тегоба у менопаузи
и ендометриозе. Циљ нашег истраживања био је да се утврдe антитуморска свој-
ства етанолног екстракта Alchemilla vulgaris agg. на ћелијској линији тумора дојке
4Т1 in vitro. Третман екстрактом Alchemilla vulgaris agg. у трајању од 72 сата је
смањио вијабилитет 4Т1 ћелија на дозно-зависан начин. Смањење вијабилно-
сти праћено је губитком пролиферативног потенцијала ћелија. Поред тога, одре-
ђени проценат 4Т1 ћелија подлегао је програмираној ћелијској смрти познатој
као апоптоза. Детектована апоптоза је праћена активацијом каспаза и додатно
потврђена типичном морфологијом нуклеуса коришћењем флуоресцентне ми-
кроскопије. Свеукупној антитуморској активности екстракта Alchemilla vulgaris
agg. доприноси и ћелијска смрт аутофагијом. Паралелно, метастатски потенцијал
ових ћелија је смањен, што је потврђено смањеном адхезијом, инвазијом, мигра-
цијом и потенцијалом ћелија да формирају колоније. Сви поменути ефекти могу
бити у корелацији са повећаном продукцијом реактивних кисеоничних и азот-
них врста детектованом након третмана. У целини, добијени резултати о делова-
њу Alchemilla vulgaris agg. на ћелије рака дојке чине ову биљку вредном пажње за
даљу евалуацију у области експерименталне онкологије.
PB  - Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine
C3  - Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
T1  - Antitumor properites of alchemilla vulgaris agg.
SP  - 129
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5290
ER  - 

@conference{
author = "Jelača, Sanja and Drača, Dijana and Dajić-Stevanović, Zora and Jovanović, Ivan and Tanić, Nikola and Mijatović, Sanja and Arsenijević, Nebojša and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "Alchemilla vulgaris is well known in traditional medicine especially for the treatment
of gynecological problems in women. Several ethnomedicinal studies for the territory
of Balkan reports its well known biological properties against many conditions such
as infertility, dysmenorrhea, cysts, menopausal complaints and endometriosis.
Concidering ethnomedicinal data on female illnesses, the aim of our study was to
determine whether ethanol extract of Alchemilla vulgaris agg. exert antitumor effect
against mouse breast cancer cells in vitro. Treatment with Alchemilla vulgaris agg. extract
decreased viability of mouse breast cancer cells (4T1) in dose-dependent manner after
72 h. The viability decrease was followed by loss of dividing potential after the treatment.
In parallel with this, certain percentage of 4T1 cells was subjected to programmed cell
death ̶ apoptosis. Detected apoptosis was followed with caspase activation while typical
apoptotic morphology of treated cells was observed by fluorescent microscopy. Apart
from inhibited cell division and induced apoptosis, decreased cell viability was due to
triggered autophagy cell death. In parallel, diminished metastatic potential of these
cells was confirmed by abrogated adhesion, invasion, migration and decreased colony
forming potential after the treatment. All mentioned effects can be connected with
enhanced production of ROS and intracellular NO after the treatment with Alchemilla
vulgaris agg. Taken together, the effect of Alchemilla vulgaris agg. against breast cancer
cells makes this plant worthwhile for further evaluation in the field of oncology., Alchemilla vulgaris је добро позната у традиционалној медицини, посебно за
лечење гинеколошких тегоба код жена. Неколико етномедицинских студија за
територију Балкана описује благотворна дејства ове биљке против различитих
патолошких стања попут неплодности, дисменореје, циста, тегоба у менопаузи
и ендометриозе. Циљ нашег истраживања био је да се утврдe антитуморска свој-
ства етанолног екстракта Alchemilla vulgaris agg. на ћелијској линији тумора дојке
4Т1 in vitro. Третман екстрактом Alchemilla vulgaris agg. у трајању од 72 сата је
смањио вијабилитет 4Т1 ћелија на дозно-зависан начин. Смањење вијабилно-
сти праћено је губитком пролиферативног потенцијала ћелија. Поред тога, одре-
ђени проценат 4Т1 ћелија подлегао је програмираној ћелијској смрти познатој
као апоптоза. Детектована апоптоза је праћена активацијом каспаза и додатно
потврђена типичном морфологијом нуклеуса коришћењем флуоресцентне ми-
кроскопије. Свеукупној антитуморској активности екстракта Alchemilla vulgaris
agg. доприноси и ћелијска смрт аутофагијом. Паралелно, метастатски потенцијал
ових ћелија је смањен, што је потврђено смањеном адхезијом, инвазијом, мигра-
цијом и потенцијалом ћелија да формирају колоније. Сви поменути ефекти могу
бити у корелацији са повећаном продукцијом реактивних кисеоничних и азот-
них врста детектованом након третмана. У целини, добијени резултати о делова-
њу Alchemilla vulgaris agg. на ћелије рака дојке чине ову биљку вредном пажње за
даљу евалуацију у области експерименталне онкологије.",
publisher = "Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine",
journal = "Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina",
title = "Antitumor properites of alchemilla vulgaris agg.",
pages = "129",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5290"
}

Jelača, S., Drača, D., Dajić-Stevanović, Z., Jovanović, I., Tanić, N., Mijatović, S., Arsenijević, N.,& Maksimović-Ivanić, D.. (2022). Antitumor properites of alchemilla vulgaris agg.. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina
Serbian Society for Immunology, Molecular Oncology and Regenerative Medicine., 129.
https://hdl.handle.net/21.15107/rcub_ibiss_5290

Jelača S, Drača D, Dajić-Stevanović Z, Jovanović I, Tanić N, Mijatović S, Arsenijević N, Maksimović-Ivanić D. Antitumor properites of alchemilla vulgaris agg.. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina. 2022;:129.
https://hdl.handle.net/21.15107/rcub_ibiss_5290 .

Jelača, Sanja, Drača, Dijana, Dajić-Stevanović, Zora, Jovanović, Ivan, Tanić, Nikola, Mijatović, Sanja, Arsenijević, Nebojša, Maksimović-Ivanić, Danijela, "Antitumor properites of alchemilla vulgaris agg." in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina (2022):129,
https://hdl.handle.net/21.15107/rcub_ibiss_5290 .

TY  - CONF
AU  - Jelača, Sanja
AU  - Mijatović, Sanja
AU  - Dajić-Stevanović, Zora
AU  - Arsenijević, Nebojša
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5286
AB  - Eryngium amethystinum is herb from Apiaceae family. It has been used as a food or in traditional medicine for the treatment of various diseases1. In the present work, we have evaluated its cytotoxic effect on a panel of human cancer cells (human breast carcinoma MCF7, human malignant melanoma A375, human colon carcinoma HCT116 and human lung cancer A549). Treatment with Eryngium amethystinum ethanol extract decreased viability of all cancer cell lines in a dose-dependent manner after 72 h. For further investigation of potential mechanism of action A549 cell line was selected. The observed viability decrease was followed by loss of dividing potential after the treatment. Aditionaly, 90% of A549 cells were subjected to programmed cell death ̶ apoptosis which was not followed with caspase activation. In paralel with this, typical apoptotic morphology of treated cells was observed by fluorescent microscopy. Apart from this decreased cell viability was due to triggered autophagic cell death. Taken together, the shown effect of Eryngium amethystinum makes this plant worthwhile for further evaluation in the field of oncology.
PB  - Belgrade: Faculty of Chemistry
C3  - Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
T1  - Antitumor properties of Eryngium amethystinum extract
SP  - 75
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5286
ER  - 

@conference{
author = "Jelača, Sanja and Mijatović, Sanja and Dajić-Stevanović, Zora and Arsenijević, Nebojša and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "Eryngium amethystinum is herb from Apiaceae family. It has been used as a food or in traditional medicine for the treatment of various diseases1. In the present work, we have evaluated its cytotoxic effect on a panel of human cancer cells (human breast carcinoma MCF7, human malignant melanoma A375, human colon carcinoma HCT116 and human lung cancer A549). Treatment with Eryngium amethystinum ethanol extract decreased viability of all cancer cell lines in a dose-dependent manner after 72 h. For further investigation of potential mechanism of action A549 cell line was selected. The observed viability decrease was followed by loss of dividing potential after the treatment. Aditionaly, 90% of A549 cells were subjected to programmed cell death ̶ apoptosis which was not followed with caspase activation. In paralel with this, typical apoptotic morphology of treated cells was observed by fluorescent microscopy. Apart from this decreased cell viability was due to triggered autophagic cell death. Taken together, the shown effect of Eryngium amethystinum makes this plant worthwhile for further evaluation in the field of oncology.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia",
title = "Antitumor properties of Eryngium amethystinum extract",
pages = "75",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5286"
}

Jelača, S., Mijatović, S., Dajić-Stevanović, Z., Arsenijević, N.,& Maksimović-Ivanić, D.. (2022). Antitumor properties of Eryngium amethystinum extract. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
Belgrade: Faculty of Chemistry., 75.
https://hdl.handle.net/21.15107/rcub_ibiss_5286

Jelača S, Mijatović S, Dajić-Stevanović Z, Arsenijević N, Maksimović-Ivanić D. Antitumor properties of Eryngium amethystinum extract. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:75.
https://hdl.handle.net/21.15107/rcub_ibiss_5286 .

Jelača, Sanja, Mijatović, Sanja, Dajić-Stevanović, Zora, Arsenijević, Nebojša, Maksimović-Ivanić, Danijela, "Antitumor properties of Eryngium amethystinum extract" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):75,
https://hdl.handle.net/21.15107/rcub_ibiss_5286 .

TY  - CONF
AU  - Markelić, Milica
AU  - Mojić, Marija
AU  - Drača, Dijana
AU  - Jelača, Sanja
AU  - Koruga, Djuro
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5285
AB  - Antioxidant and anticancer properties of fullerene C60 and especially of its polyhydroxylated, water soluble derivatives (fullerols) make them appealing for biomedical applications. In order to analyse antitumor effects of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC)1, second generation of fullerol, melanoma cells of different intracellular features and invasive potential (B16, B16-F10, A375) were treated with 3HFWC in various concentrations (0.19-100 μg/ml) for 24, 48 and 72h. Subsequently, syngeneic murine melanoma model was used (oral 3HFWC intake, 0.15 g/l). The most prominent effect of 3HFWC, both in vitro and in vivo2, was induction of cell senescence, followed by decreased proliferative capacity and tumor growth inhibition. Senescent cells remained viable in vitro, but lost ability to divide and decreased metabolic activity, due to mitochondria alterations. Our findings demonstrate pro-senescence approach in antitumor therapy which is suggested to be less aggressive than the conventional strategies based on cancer cell killing, frequently followed by compensatory proliferation and subsequent tumor progression.
PB  - Belgrade: Faculty of Chemistry
C3  - Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
T1  - Pro-senescent effects of hyper-harmonized hydroxylated fullerene water complex in melanoma
SP  - 95
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5285
ER  - 

@conference{
author = "Markelić, Milica and Mojić, Marija and Drača, Dijana and Jelača, Sanja and Koruga, Djuro and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "Antioxidant and anticancer properties of fullerene C60 and especially of its polyhydroxylated, water soluble derivatives (fullerols) make them appealing for biomedical applications. In order to analyse antitumor effects of Hyper-Harmonized Hydroxylated Fullerene Water Complex (3HFWC)1, second generation of fullerol, melanoma cells of different intracellular features and invasive potential (B16, B16-F10, A375) were treated with 3HFWC in various concentrations (0.19-100 μg/ml) for 24, 48 and 72h. Subsequently, syngeneic murine melanoma model was used (oral 3HFWC intake, 0.15 g/l). The most prominent effect of 3HFWC, both in vitro and in vivo2, was induction of cell senescence, followed by decreased proliferative capacity and tumor growth inhibition. Senescent cells remained viable in vitro, but lost ability to divide and decreased metabolic activity, due to mitochondria alterations. Our findings demonstrate pro-senescence approach in antitumor therapy which is suggested to be less aggressive than the conventional strategies based on cancer cell killing, frequently followed by compensatory proliferation and subsequent tumor progression.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia",
title = "Pro-senescent effects of hyper-harmonized hydroxylated fullerene water complex in melanoma",
pages = "95",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5285"
}

Markelić, M., Mojić, M., Drača, D., Jelača, S., Koruga, D., Mijatović, S.,& Maksimović-Ivanić, D.. (2022). Pro-senescent effects of hyper-harmonized hydroxylated fullerene water complex in melanoma. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia
Belgrade: Faculty of Chemistry., 95.
https://hdl.handle.net/21.15107/rcub_ibiss_5285

Markelić M, Mojić M, Drača D, Jelača S, Koruga D, Mijatović S, Maksimović-Ivanić D. Pro-senescent effects of hyper-harmonized hydroxylated fullerene water complex in melanoma. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:95.
https://hdl.handle.net/21.15107/rcub_ibiss_5285 .

Markelić, Milica, Mojić, Marija, Drača, Dijana, Jelača, Sanja, Koruga, Djuro, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Pro-senescent effects of hyper-harmonized hydroxylated fullerene water complex in melanoma" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):95,
https://hdl.handle.net/21.15107/rcub_ibiss_5285 .

TY  - CONF
AU  - Kazimir, Aleksandr
AU  - Schwarze, Benedikt
AU  - Jelača, Sanja
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
PY  - 2022
UR  - https://eurobic16.sciencesconf.org/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5318
AB  - Tamoxifen (Scheme 1, 1) is historically well known for its successful application in the therapy of
the oestrogen receptor positive (ERα+) breast cancer.1
In this study, we combine a tamoxifenbased ligand2
(Scheme 1, 3) with transition metal complex moieties of platinum(II), palladium(II),
copper(II), and nickel(II)3
containing chlorides (Scheme 1, 4-6) or a bulky, hydrophobic and stable
nido-dicarborate ligand (Scheme 1, 7-9). We investigated the anticancer activity of the
compounds 2-9 in in vitro cell assays. The incorporation of a 2,2’-bipyridine unit into a tamoxifen-inspired structure 3 increases the
cytotoxic activity compared to compound 2 against several cell lines including ERα+ human
glioblastoma (U251), breast adenocarcinoma (MCF-7, MDA-MB-361) and triple negative (ERα−)
MDA-MB-231. The formation of PtII and PdII chloride complexes (4 and 5) insignificantly improve
the activity compared to ligand 3. The ability of the CuII chloride moiety for ligand exchange in
solution explains the significant rise of the cytotoxicity of 6 compared to 4 and 5. However, the
incorporation of a nido-carborate dianion into Pt and Ni complexes (7 and 9) neutralised on
average their toxicity towards all studied cell lines, except compound 8 which was active against
U251 and MDA-MB-231. The observed cytotoxicity data of compounds 3-6 and 8 against MDAMB-231 (ERα−) suggest other off-target mechanisms rather than only ERα inhibition which is
usual for metallodrugs.
PB  - Society of Biological Inorganic Chemistry
C3  - 16th European Biological Inorganic Chemistry Conference: EuroBIC-16; 2022 Jul 17-21; Grenoble, France
T1  - Tamoxifen-based compounds in the breast cancer therapy
SP  - BI31
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5318
ER  - 

@conference{
author = "Kazimir, Aleksandr and Schwarze, Benedikt and Jelača, Sanja and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie",
year = "2022",
abstract = "Tamoxifen (Scheme 1, 1) is historically well known for its successful application in the therapy of
the oestrogen receptor positive (ERα+) breast cancer.1
In this study, we combine a tamoxifenbased ligand2
(Scheme 1, 3) with transition metal complex moieties of platinum(II), palladium(II),
copper(II), and nickel(II)3
containing chlorides (Scheme 1, 4-6) or a bulky, hydrophobic and stable
nido-dicarborate ligand (Scheme 1, 7-9). We investigated the anticancer activity of the
compounds 2-9 in in vitro cell assays. The incorporation of a 2,2’-bipyridine unit into a tamoxifen-inspired structure 3 increases the
cytotoxic activity compared to compound 2 against several cell lines including ERα+ human
glioblastoma (U251), breast adenocarcinoma (MCF-7, MDA-MB-361) and triple negative (ERα−)
MDA-MB-231. The formation of PtII and PdII chloride complexes (4 and 5) insignificantly improve
the activity compared to ligand 3. The ability of the CuII chloride moiety for ligand exchange in
solution explains the significant rise of the cytotoxicity of 6 compared to 4 and 5. However, the
incorporation of a nido-carborate dianion into Pt and Ni complexes (7 and 9) neutralised on
average their toxicity towards all studied cell lines, except compound 8 which was active against
U251 and MDA-MB-231. The observed cytotoxicity data of compounds 3-6 and 8 against MDAMB-231 (ERα−) suggest other off-target mechanisms rather than only ERα inhibition which is
usual for metallodrugs.",
publisher = "Society of Biological Inorganic Chemistry",
journal = "16th European Biological Inorganic Chemistry Conference: EuroBIC-16; 2022 Jul 17-21; Grenoble, France",
title = "Tamoxifen-based compounds in the breast cancer therapy",
pages = "BI31",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5318"
}

Kazimir, A., Schwarze, B., Jelača, S., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2022). Tamoxifen-based compounds in the breast cancer therapy. in 16th European Biological Inorganic Chemistry Conference: EuroBIC-16; 2022 Jul 17-21; Grenoble, France
Society of Biological Inorganic Chemistry., BI31.
https://hdl.handle.net/21.15107/rcub_ibiss_5318

Kazimir A, Schwarze B, Jelača S, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Tamoxifen-based compounds in the breast cancer therapy. in 16th European Biological Inorganic Chemistry Conference: EuroBIC-16; 2022 Jul 17-21; Grenoble, France. 2022;:BI31.
https://hdl.handle.net/21.15107/rcub_ibiss_5318 .

Kazimir, Aleksandr, Schwarze, Benedikt, Jelača, Sanja, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Tamoxifen-based compounds in the breast cancer therapy" in 16th European Biological Inorganic Chemistry Conference: EuroBIC-16; 2022 Jul 17-21; Grenoble, France (2022):BI31,
https://hdl.handle.net/21.15107/rcub_ibiss_5318 .

TY  - JOUR
AU  - Vojnović-Milutinović, Danijela
AU  - Teofilović, Ana
AU  - Veličković, Nataša
AU  - Brkljačić, Jelena
AU  - Jelača, Sanja
AU  - Đorđević, Ana
AU  - Macut, Đuro
PY  - 2021
UR  - https://doi.org/10.1007/s12020-020-02600-1
UR  - http://www.ncbi.nlm.nih.gov/pubmed/33449293
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4146
AB  - PURPOSE Polycystic ovary syndrome (PCOS) is a complex reproductive disorder often associated with obesity, insulin resistance, and dyslipidemia. Hormonal changes in PCOS may also include altered glucocorticoid signaling. Our aim was to examine whether alterations in hepatic glucocorticoid signaling are associated with disturbances of glucose and lipid metabolism in animal model of PCOS. METHODS Female rats, 3 weeks old, were subcutaneously implanted with 5α-dihydrotestosterone (DHT) or placebo pellets for 90 days to induce PCOS. Expression of 11β-hydroxysteroid dehydrogenase 1 (11βHSD1) and A-ring reductases (5α and 5β), as well as intracellular distribution of glucocorticoid receptor (GR) and expression of its regulated genes were examined in the liver. Proteins of hepatic lipid and carbohydrate metabolism and markers of inflammation were also assessed. RESULTS DHT treatment induced increase in body and liver mass, as well as in triglycerides and free fatty acids levels in plasma. Elevation of 11βHSD1 and reduction of 5α-reductase expression was observed together with increased hepatic corticosterone concentration and nuclear GR activation. Induced expression of Krüppel-like factor 15 and decreased expression of genes for proinflammatory cytokines and de novo lipogenesis (DNL) were detected in the liver of DHT-treated rats, while DNL regulators and proinflammatory markers were not changed. However, increased mRNA levels of stearoyl-CoA desaturase and apolipoprotein B were observed in DHT animals. CONCLUSIONS DHT treatment stimulated hepatic glucocorticoid prereceptor metabolism through increased corticosterone availability which is associated with enhanced GR activation. This does not affect gluconeogenesis and DNL, but could be linked to stimulated triglyceride synthesis and hypertriglyceridemia.
PB  - Springer
T2  - Endocrine
T1  - Glucocorticoid signaling and lipid metabolism disturbances in the liver of rats treated with 5α-dihydrotestosterone in an animal model of polycystic ovary syndrome.
DO  - 10.1007/s12020-020-02600-1
ER  - 

@article{
author = "Vojnović-Milutinović, Danijela and Teofilović, Ana and Veličković, Nataša and Brkljačić, Jelena and Jelača, Sanja and Đorđević, Ana and Macut, Đuro",
year = "2021",
abstract = "PURPOSE Polycystic ovary syndrome (PCOS) is a complex reproductive disorder often associated with obesity, insulin resistance, and dyslipidemia. Hormonal changes in PCOS may also include altered glucocorticoid signaling. Our aim was to examine whether alterations in hepatic glucocorticoid signaling are associated with disturbances of glucose and lipid metabolism in animal model of PCOS. METHODS Female rats, 3 weeks old, were subcutaneously implanted with 5α-dihydrotestosterone (DHT) or placebo pellets for 90 days to induce PCOS. Expression of 11β-hydroxysteroid dehydrogenase 1 (11βHSD1) and A-ring reductases (5α and 5β), as well as intracellular distribution of glucocorticoid receptor (GR) and expression of its regulated genes were examined in the liver. Proteins of hepatic lipid and carbohydrate metabolism and markers of inflammation were also assessed. RESULTS DHT treatment induced increase in body and liver mass, as well as in triglycerides and free fatty acids levels in plasma. Elevation of 11βHSD1 and reduction of 5α-reductase expression was observed together with increased hepatic corticosterone concentration and nuclear GR activation. Induced expression of Krüppel-like factor 15 and decreased expression of genes for proinflammatory cytokines and de novo lipogenesis (DNL) were detected in the liver of DHT-treated rats, while DNL regulators and proinflammatory markers were not changed. However, increased mRNA levels of stearoyl-CoA desaturase and apolipoprotein B were observed in DHT animals. CONCLUSIONS DHT treatment stimulated hepatic glucocorticoid prereceptor metabolism through increased corticosterone availability which is associated with enhanced GR activation. This does not affect gluconeogenesis and DNL, but could be linked to stimulated triglyceride synthesis and hypertriglyceridemia.",
publisher = "Springer",
journal = "Endocrine",
title = "Glucocorticoid signaling and lipid metabolism disturbances in the liver of rats treated with 5α-dihydrotestosterone in an animal model of polycystic ovary syndrome.",
doi = "10.1007/s12020-020-02600-1"
}

Vojnović-Milutinović, D., Teofilović, A., Veličković, N., Brkljačić, J., Jelača, S., Đorđević, A.,& Macut, Đ.. (2021). Glucocorticoid signaling and lipid metabolism disturbances in the liver of rats treated with 5α-dihydrotestosterone in an animal model of polycystic ovary syndrome.. in Endocrine
Springer..
https://doi.org/10.1007/s12020-020-02600-1

Vojnović-Milutinović D, Teofilović A, Veličković N, Brkljačić J, Jelača S, Đorđević A, Macut Đ. Glucocorticoid signaling and lipid metabolism disturbances in the liver of rats treated with 5α-dihydrotestosterone in an animal model of polycystic ovary syndrome.. in Endocrine. 2021;.
doi:10.1007/s12020-020-02600-1 .

Vojnović-Milutinović, Danijela, Teofilović, Ana, Veličković, Nataša, Brkljačić, Jelena, Jelača, Sanja, Đorđević, Ana, Macut, Đuro, "Glucocorticoid signaling and lipid metabolism disturbances in the liver of rats treated with 5α-dihydrotestosterone in an animal model of polycystic ovary syndrome." in Endocrine (2021),
https://doi.org/10.1007/s12020-020-02600-1 . .

TY  - CONF
AU  - Jelača, Sanja
AU  - Drača, Dijana
AU  - Dajić Stevanović, Zora
AU  - Jovanović, Ivan
AU  - Pavlović, Slađana
AU  - Gajović, Nevena
AU  - Mijatović, Sanja
AU  - Arsenijević, Nebojša
AU  - Maksimović-Ivanić, Danijela
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4432
UR  - https://onlinelibrary.wiley.com/toc/15214141/2021/51/S1
AB  - Several ethnobotanical reports on Alchemilla vulgaris L. pointed out diverse biological properties against problems such as dysmenorrhea, pruritus vulvae, menopausal complaints 
as  well  as  related  diseases  in  women.  Also  previous  studies  have  shown  that  Alchemilla  vulgaris  L.  extracts  are  exhibiting  antiinflammatory,  antioxidant,  wound  healing  and 
neuroprotective activity. The aim of this study was to evaluate the direct effect of Alchemilla vulgaris L. ethanol extract against melanoma cells in vitro and in vivo, as well as its effect 
on tumor microenvironment ex vivo. This study was performed on two different mouse melanoma cell lines, B16 and B16F10, and on syngeneic mouse melanoma model in vivo. 
Obtained results revealed dose‐dependent decrease of cell viability after 72 h‐ treatment with Alchemilla vulgaris L. extract. The observed effect was followed by loss of dividing 
potential in both tested cell lines. In parallel with this, certain percentage of B16F10 cells was subjected to programmed cell death in a caspase independent manner while in B16 cells 
estimation of the presence of autophagosomes by flow cytometry has shown that autophagy is occurring after the treatment and it is shown to be mechanism of death. Concerning in 
vivo studies Alchemilla vulgaris L. extract significantly reduced tumor growth in B16 melanoma model partly through stimulation of antitumor immune responce. It altered dendritic 
cells phenotype which activated cytotoxic and CD4+ T lymphocytes to successfully destroy tumor cells. In summary, these data indicate that Alchemilla vulgaris L. is valuable of further 
investigation in the field of experimental oncology.
PB  - Wiley‐VCH GmbH
C3  - 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
T1  - Multiple effects of Alchemilla vulgaris L. extract on melanoma cells and tumor microenvironment
IS  - Suppl 1
VL  - 51
DO  - 10.1002/eji.202170200
SP  - 352
ER  - 

@conference{
author = "Jelača, Sanja and Drača, Dijana and Dajić Stevanović, Zora and Jovanović, Ivan and Pavlović, Slađana and Gajović, Nevena and Mijatović, Sanja and Arsenijević, Nebojša and Maksimović-Ivanić, Danijela",
year = "2021",
abstract = "Several ethnobotanical reports on Alchemilla vulgaris L. pointed out diverse biological properties against problems such as dysmenorrhea, pruritus vulvae, menopausal complaints 
as  well  as  related  diseases  in  women.  Also  previous  studies  have  shown  that  Alchemilla  vulgaris  L.  extracts  are  exhibiting  antiinflammatory,  antioxidant,  wound  healing  and 
neuroprotective activity. The aim of this study was to evaluate the direct effect of Alchemilla vulgaris L. ethanol extract against melanoma cells in vitro and in vivo, as well as its effect 
on tumor microenvironment ex vivo. This study was performed on two different mouse melanoma cell lines, B16 and B16F10, and on syngeneic mouse melanoma model in vivo. 
Obtained results revealed dose‐dependent decrease of cell viability after 72 h‐ treatment with Alchemilla vulgaris L. extract. The observed effect was followed by loss of dividing 
potential in both tested cell lines. In parallel with this, certain percentage of B16F10 cells was subjected to programmed cell death in a caspase independent manner while in B16 cells 
estimation of the presence of autophagosomes by flow cytometry has shown that autophagy is occurring after the treatment and it is shown to be mechanism of death. Concerning in 
vivo studies Alchemilla vulgaris L. extract significantly reduced tumor growth in B16 melanoma model partly through stimulation of antitumor immune responce. It altered dendritic 
cells phenotype which activated cytotoxic and CD4+ T lymphocytes to successfully destroy tumor cells. In summary, these data indicate that Alchemilla vulgaris L. is valuable of further 
investigation in the field of experimental oncology.",
publisher = "Wiley‐VCH GmbH",
journal = "6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting",
title = "Multiple effects of Alchemilla vulgaris L. extract on melanoma cells and tumor microenvironment",
number = "Suppl 1",
volume = "51",
doi = "10.1002/eji.202170200",
pages = "352"
}

Jelača, S., Drača, D., Dajić Stevanović, Z., Jovanović, I., Pavlović, S., Gajović, N., Mijatović, S., Arsenijević, N.,& Maksimović-Ivanić, D.. (2021). Multiple effects of Alchemilla vulgaris L. extract on melanoma cells and tumor microenvironment. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
Wiley‐VCH GmbH., 51(Suppl 1), 352.
https://doi.org/10.1002/eji.202170200

Jelača S, Drača D, Dajić Stevanović Z, Jovanović I, Pavlović S, Gajović N, Mijatović S, Arsenijević N, Maksimović-Ivanić D. Multiple effects of Alchemilla vulgaris L. extract on melanoma cells and tumor microenvironment. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting. 2021;51(Suppl 1):352.
doi:10.1002/eji.202170200 .

Jelača, Sanja, Drača, Dijana, Dajić Stevanović, Zora, Jovanović, Ivan, Pavlović, Slađana, Gajović, Nevena, Mijatović, Sanja, Arsenijević, Nebojša, Maksimović-Ivanić, Danijela, "Multiple effects of Alchemilla vulgaris L. extract on melanoma cells and tumor microenvironment" in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting, 51, no. Suppl 1 (2021):352,
https://doi.org/10.1002/eji.202170200 . .

TY  - CONF
AU  - Jelača, Sanja
AU  - Drača, Dijana
AU  - Dajić Stevanović, Zora
AU  - Mijatović, Sanja
AU  - Jovanović, Ivan
AU  - Jovanović, Marina
AU  - Jurišević, Marina
AU  - Arsenijević, Nebojša
AU  - Maksimović-Ivanić, Danijela
PY  - 2021
UR  - https://onlinelibrary.wiley.com/toc/15214141/2021/51/S1
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4426
AB  - Alchemilla vulgaris L. has long history of usage in folk medicine especially against gynecological problems. Ethnomedicinal reports for the territory of Balkan are mentioning its well 
known biological properties against dysmenorrhea, menopausal complaints, infertility, cysts and endometriosis. Based on ethnomedicinal data on female illnesses, the objective of 
our study was to determine the effect of Alchemilla vulgaris L. ethanol extract against breast cancer cells in vitro and in vivo. Our results have showed remarkable viability decrease 
of mouse (4T1) breast cancer cells in dose‐dependent manner after the treatment with Alchemilla vulgaris L. extract. Strong inhibition of cell prolifertion was observed in treated 
cells. In parallel with this, different types of cell death was found. Certain percentage of 4T1 cells was subjected to programmed cell death‐apoptosis which was followed with caspase 
activation and confirmed by fluorescent microscopy observing tipical morphologicas features of apoptosis in treated culture. Estimation of the presence of autophagosomes shown 
that autophagy contributing  to  the cytotoxicity of the  treatment. Also, enhanced production of ROS and intracellular NO after treatment with Alchemilla vulgaris L. was  found. 
In parallel, metastatic potential of this cells is diminished. Apart from the direct effect of A. Vulgaris L. extract on tumor cells, strong potentiation of antitumor immune responce 
manifested dominantly through enhanced accumulation of activated dendritic cells and subsequently CD8+ T cells in spleen and tumor microenvironment. Above briefly described 
mode of action of Alchemilla vulgaris L. against breast cancer cells makes this plant worthwhile for further evaluation in the field of oncology.
PB  - Wiley‐VCH GmbH
C3  - 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
T1  - Antitumor potential of Alchemilla vulgaris L. in ortotopic mouse breast cancer model
IS  - Suppl 1
VL  - 51
DO  - 10.1002/eji.202170200
SP  - 351
ER  - 

@conference{
author = "Jelača, Sanja and Drača, Dijana and Dajić Stevanović, Zora and Mijatović, Sanja and Jovanović, Ivan and Jovanović, Marina and Jurišević, Marina and Arsenijević, Nebojša and Maksimović-Ivanić, Danijela",
year = "2021",
abstract = "Alchemilla vulgaris L. has long history of usage in folk medicine especially against gynecological problems. Ethnomedicinal reports for the territory of Balkan are mentioning its well 
known biological properties against dysmenorrhea, menopausal complaints, infertility, cysts and endometriosis. Based on ethnomedicinal data on female illnesses, the objective of 
our study was to determine the effect of Alchemilla vulgaris L. ethanol extract against breast cancer cells in vitro and in vivo. Our results have showed remarkable viability decrease 
of mouse (4T1) breast cancer cells in dose‐dependent manner after the treatment with Alchemilla vulgaris L. extract. Strong inhibition of cell prolifertion was observed in treated 
cells. In parallel with this, different types of cell death was found. Certain percentage of 4T1 cells was subjected to programmed cell death‐apoptosis which was followed with caspase 
activation and confirmed by fluorescent microscopy observing tipical morphologicas features of apoptosis in treated culture. Estimation of the presence of autophagosomes shown 
that autophagy contributing  to  the cytotoxicity of the  treatment. Also, enhanced production of ROS and intracellular NO after treatment with Alchemilla vulgaris L. was  found. 
In parallel, metastatic potential of this cells is diminished. Apart from the direct effect of A. Vulgaris L. extract on tumor cells, strong potentiation of antitumor immune responce 
manifested dominantly through enhanced accumulation of activated dendritic cells and subsequently CD8+ T cells in spleen and tumor microenvironment. Above briefly described 
mode of action of Alchemilla vulgaris L. against breast cancer cells makes this plant worthwhile for further evaluation in the field of oncology.",
publisher = "Wiley‐VCH GmbH",
journal = "6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting",
title = "Antitumor potential of Alchemilla vulgaris L. in ortotopic mouse breast cancer model",
number = "Suppl 1",
volume = "51",
doi = "10.1002/eji.202170200",
pages = "351"
}

Jelača, S., Drača, D., Dajić Stevanović, Z., Mijatović, S., Jovanović, I., Jovanović, M., Jurišević, M., Arsenijević, N.,& Maksimović-Ivanić, D.. (2021). Antitumor potential of Alchemilla vulgaris L. in ortotopic mouse breast cancer model. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting
Wiley‐VCH GmbH., 51(Suppl 1), 351.
https://doi.org/10.1002/eji.202170200

Jelača S, Drača D, Dajić Stevanović Z, Mijatović S, Jovanović I, Jovanović M, Jurišević M, Arsenijević N, Maksimović-Ivanić D. Antitumor potential of Alchemilla vulgaris L. in ortotopic mouse breast cancer model. in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting. 2021;51(Suppl 1):351.
doi:10.1002/eji.202170200 .

Jelača, Sanja, Drača, Dijana, Dajić Stevanović, Zora, Mijatović, Sanja, Jovanović, Ivan, Jovanović, Marina, Jurišević, Marina, Arsenijević, Nebojša, Maksimović-Ivanić, Danijela, "Antitumor potential of Alchemilla vulgaris L. in ortotopic mouse breast cancer model" in 6th European Congress of Immunology; 2021 Sep 1-4; Virtual Meeting, 51, no. Suppl 1 (2021):351,
https://doi.org/10.1002/eji.202170200 . .