TY  - JOUR
AU  - Bovan, Dijana
AU  - Krajnović, Tamara
AU  - Vuković, Nenad L.
AU  - Vukić, Milena D.
AU  - Mijatović, Sanja
AU  - Tanić, Nikola
AU  - Arsenijević, Nebojša
AU  - Maksimović-Ivanić, Danijela
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6576
AB  - Background: Shikonin is a naturally occurring naphthoquinone found in the roots of several genera of the Boraginaceae family, widely known for its numerous biological activities, such as antiinflammatory, antioxidant, antimicrobial and anticancer. In this study, the antitumor effect of six naphthoquinones isolated from the roots of Onosma visianii was evaluated using two cell lines, mouse melanoma B16 and highly aggressive rat glioma cell line C6. 
Methods and results: All examined shikonins dose-dependently decreased the viability of tested cells, with compounds 5 and 6 being the most potent ones and hence subjected to further analysis. The diminished viability of B16 melanoma cells was in correlation with detected caspase-mediated apoptosis. Importantly, observed altered cell morphology along with the loss of dividing potential upon exposure to both shikonins implied reprogram of B16 cell phenotype. Elevated expression of myelin basic protein indicated the acquirement of Schwann‐like cell phenotype, while detected autophagy might be connected to this phenomenon. On the contrary, upon exposure to both agents, C6 cells underwent specific cell death—anoikis, provoked by detachment from the extracellular matrix and compromised integrin signaling. Oppositely to compound 5, compound 6 realized anoikis in a caspase-independent manner and under sustained ERK1/2 activation, indicating the deviation from standard proanoikis signaling. 
Conclusions: Herein, we have pointed out the diversity and novelty in the mode of action of shikonin derivatives depending on the tumor cell features, which represents a good platform for new investigations of these promising natural compounds.
PB  - Springer Nature
T2  - Molecular Biology Reports
T1  - Anoikis and cancer cell differentiation: novel modes of shikonin derivatives anticancer action in vitro
IS  - 1
VL  - 51
DO  - 10.1007/s11033-023-09093-x
SP  - 218
ER  - 

@article{
author = "Bovan, Dijana and Krajnović, Tamara and Vuković, Nenad L. and Vukić, Milena D. and Mijatović, Sanja and Tanić, Nikola and Arsenijević, Nebojša and Maksimović-Ivanić, Danijela",
year = "2024",
abstract = "Background: Shikonin is a naturally occurring naphthoquinone found in the roots of several genera of the Boraginaceae family, widely known for its numerous biological activities, such as antiinflammatory, antioxidant, antimicrobial and anticancer. In this study, the antitumor effect of six naphthoquinones isolated from the roots of Onosma visianii was evaluated using two cell lines, mouse melanoma B16 and highly aggressive rat glioma cell line C6. 
Methods and results: All examined shikonins dose-dependently decreased the viability of tested cells, with compounds 5 and 6 being the most potent ones and hence subjected to further analysis. The diminished viability of B16 melanoma cells was in correlation with detected caspase-mediated apoptosis. Importantly, observed altered cell morphology along with the loss of dividing potential upon exposure to both shikonins implied reprogram of B16 cell phenotype. Elevated expression of myelin basic protein indicated the acquirement of Schwann‐like cell phenotype, while detected autophagy might be connected to this phenomenon. On the contrary, upon exposure to both agents, C6 cells underwent specific cell death—anoikis, provoked by detachment from the extracellular matrix and compromised integrin signaling. Oppositely to compound 5, compound 6 realized anoikis in a caspase-independent manner and under sustained ERK1/2 activation, indicating the deviation from standard proanoikis signaling. 
Conclusions: Herein, we have pointed out the diversity and novelty in the mode of action of shikonin derivatives depending on the tumor cell features, which represents a good platform for new investigations of these promising natural compounds.",
publisher = "Springer Nature",
journal = "Molecular Biology Reports",
title = "Anoikis and cancer cell differentiation: novel modes of shikonin derivatives anticancer action in vitro",
number = "1",
volume = "51",
doi = "10.1007/s11033-023-09093-x",
pages = "218"
}

Bovan, D., Krajnović, T., Vuković, N. L., Vukić, M. D., Mijatović, S., Tanić, N., Arsenijević, N.,& Maksimović-Ivanić, D.. (2024). Anoikis and cancer cell differentiation: novel modes of shikonin derivatives anticancer action in vitro. in Molecular Biology Reports
Springer Nature., 51(1), 218.
https://doi.org/10.1007/s11033-023-09093-x

Bovan D, Krajnović T, Vuković NL, Vukić MD, Mijatović S, Tanić N, Arsenijević N, Maksimović-Ivanić D. Anoikis and cancer cell differentiation: novel modes of shikonin derivatives anticancer action in vitro. in Molecular Biology Reports. 2024;51(1):218.
doi:10.1007/s11033-023-09093-x .

Bovan, Dijana, Krajnović, Tamara, Vuković, Nenad L., Vukić, Milena D., Mijatović, Sanja, Tanić, Nikola, Arsenijević, Nebojša, Maksimović-Ivanić, Danijela, "Anoikis and cancer cell differentiation: novel modes of shikonin derivatives anticancer action in vitro" in Molecular Biology Reports, 51, no. 1 (2024):218,
https://doi.org/10.1007/s11033-023-09093-x . .

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  - CONF
AU  - Krajnović, Tamara
AU  - Bovan, Dijana
AU  - Vuković, Nenad L.
AU  - Vukić, Milena D.
AU  - Mijatović, Sanja
AU  - Tanić, Nikola
AU  - Arsenijević, Nebojša
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6267
AB  - Background: Shikonins are naturally occurring naphthoquinones found in the roots of several genera of the Boraginaceae family, widely known for their antiinflammatory, antioxidant, antimicrobial, and anticancer properties. This study aimed to investigate the antitumor potential of six shikonins isolated from the roots of Onosma visianii against highly aggressive rat glioma cell line C6 and to explore the mechanisms involved. Material and Methods: Cell viability was estimated by MTT and CV assays. Cell death, proliferation rate, and caspase activity were assessed using flow cytometric analysis of annexin V-FITC/propidium iodide, CFSE, and ApoStat staining, respectively. Fluorescent microscopy of propidium iodide-stained cells was employed for the detection of nuclear morphology. To evaluate the viability of detached cells, an acidic phosphatase assay was used. The cells’ property to adhere was assessed by cell adhesion assay while western blot was engaged to measure the expression of relevant proteins responsible for the observed phenomenon. Results and Conclusions: All examined shikonins dose-dependently decreased the viability of C6 cells, with compounds 5 and 6 being the most potent ones. Compound 5 had a more profound effect on the proliferation rate of C6 cells than compound 6, resulting in almost 70% of inhibition of cell division. Additionally, compound 5, but not compound 6 generated a significant number of early and late apoptotic cells in treated cultures as detected by flow cytometry. In collision with this, typical morphological signs of apoptotic cells were not observed, and fluorescent microscopy revealed only the presence of enlarged nuclei. This paradox was resolved by the discovery of massive detached cell presence, indicating that glioma cells underwent anoikis, a cell attachment-dependent programmed cell death, in response to treatment with both agents. Decreased ability of C6 cells to adhere to the extracellular matrix and compromised integrin signaling was further confirmed by adhesion assay and western blot, respectively. Interestingly, while compound 5 triggered caspase-mediated anoikis, compound 6 realized anoikis in a caspase-independent manner and under sustained ERK1/2 activation, indicating the deviation from standard proanoikis signaling. This study represents the first proof of shikonin derivatives’ strong anticancer potential realized through the induction of anoikis of highly proliferative and invasive malignant glioma cells.
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  - Anoikis as a novel mode of shikonin derivatives anticancer action on C6 glioma cells
SP  - 98
EP  - 99
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6267
ER  - 

@conference{
author = "Krajnović, Tamara and Bovan, Dijana and Vuković, Nenad L. and Vukić, Milena D. and Mijatović, Sanja and Tanić, Nikola and Arsenijević, Nebojša and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Background: Shikonins are naturally occurring naphthoquinones found in the roots of several genera of the Boraginaceae family, widely known for their antiinflammatory, antioxidant, antimicrobial, and anticancer properties. This study aimed to investigate the antitumor potential of six shikonins isolated from the roots of Onosma visianii against highly aggressive rat glioma cell line C6 and to explore the mechanisms involved. Material and Methods: Cell viability was estimated by MTT and CV assays. Cell death, proliferation rate, and caspase activity were assessed using flow cytometric analysis of annexin V-FITC/propidium iodide, CFSE, and ApoStat staining, respectively. Fluorescent microscopy of propidium iodide-stained cells was employed for the detection of nuclear morphology. To evaluate the viability of detached cells, an acidic phosphatase assay was used. The cells’ property to adhere was assessed by cell adhesion assay while western blot was engaged to measure the expression of relevant proteins responsible for the observed phenomenon. Results and Conclusions: All examined shikonins dose-dependently decreased the viability of C6 cells, with compounds 5 and 6 being the most potent ones. Compound 5 had a more profound effect on the proliferation rate of C6 cells than compound 6, resulting in almost 70% of inhibition of cell division. Additionally, compound 5, but not compound 6 generated a significant number of early and late apoptotic cells in treated cultures as detected by flow cytometry. In collision with this, typical morphological signs of apoptotic cells were not observed, and fluorescent microscopy revealed only the presence of enlarged nuclei. This paradox was resolved by the discovery of massive detached cell presence, indicating that glioma cells underwent anoikis, a cell attachment-dependent programmed cell death, in response to treatment with both agents. Decreased ability of C6 cells to adhere to the extracellular matrix and compromised integrin signaling was further confirmed by adhesion assay and western blot, respectively. Interestingly, while compound 5 triggered caspase-mediated anoikis, compound 6 realized anoikis in a caspase-independent manner and under sustained ERK1/2 activation, indicating the deviation from standard proanoikis signaling. This study represents the first proof of shikonin derivatives’ strong anticancer potential realized through the induction of anoikis of highly proliferative and invasive malignant glioma cells.",
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 = "Anoikis as a novel mode of shikonin derivatives anticancer action on C6 glioma cells",
pages = "98-99",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6267"
}

Krajnović, T., Bovan, D., Vuković, N. L., Vukić, M. D., Mijatović, S., Tanić, N., Arsenijević, N.,& Maksimović-Ivanić, D.. (2023). Anoikis as a novel mode of shikonin derivatives anticancer action on C6 glioma cells. 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., 98-99.
https://hdl.handle.net/21.15107/rcub_ibiss_6267

Krajnović T, Bovan D, Vuković NL, Vukić MD, Mijatović S, Tanić N, Arsenijević N, Maksimović-Ivanić D. Anoikis as a novel mode of shikonin derivatives anticancer action on C6 glioma cells. 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;:98-99.
https://hdl.handle.net/21.15107/rcub_ibiss_6267 .

Krajnović, Tamara, Bovan, Dijana, Vuković, Nenad L., Vukić, Milena D., Mijatović, Sanja, Tanić, Nikola, Arsenijević, Nebojša, Maksimović-Ivanić, Danijela, "Anoikis as a novel mode of shikonin derivatives anticancer action on C6 glioma cells" 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):98-99,
https://hdl.handle.net/21.15107/rcub_ibiss_6267 .

TY  - JOUR
AU  - Richter, Stefan
AU  - Lönnecke, Peter
AU  - Bovan, Dijana
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Kaluđerović, Goran N.
AU  - Hey-Hawkins, Evamarie
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6265
AB  - The coordination behavior of three ligand precursors 2-[(2-pyridinylmethyl)amino]acetic acid hydrochloride, 4-[(2-pyridinylmethyl)amino]benzoic acid hydrochloride and 4-{[2-(pyridin-2-ylmethylamino)ethylamino]methyl}benzoic acid hydrochloride, HL1∙HCl–HL3∙HCl, respectively, in copper(II) complexes is described. The complexes were characterized by elemental analysis, ESI mass spectrometry and IR spectroscopy, as well as X-ray structural analysis. The reaction of copper(II) with HL1∙HCl in methanol afforded the polymeric complex [{Cu(µ-Cl)2(MeL1-κ2N,N’)}n] (1) featuring the methyl ester of L1 (MeL1). With HL2∙HCl or HL3∙HCl, the dimeric complex [{CuCl(µ-Cl)(HL2-κ2N,N’)}2] (2) or the mononuclear complex [CuCl2(HL3-κ3N,N’,N’’)] (3) were obtained. All complexes exhibited square-pyramidal geometries. In 1, polymeric chains are formed through bridging chlorido ligands without typical hydrogen bonding interaction. Contrarily, the COOH group in 2 is participating in the formation of intermolecular hydrogen bonding forming a supramolecular structure. In 3, intermolecular hydrogen bonding (Cl…O) leads to a 1-D polymeric structure. The copper(II) complex 2 diminished viability of human 8505C, MCF-7, 518A2 and SW480 cell lines. The tumoricidal effect of 2 was realized mainly through caspase-mediated apoptosis.
PB  - Belgrade: Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Square-pyramidal mononuclear, dinuclear and polymeric copper(II) complexes with (2-pyridinylmethyl)amino derivatives
DO  - 10.2298/JSC230818072R
ER  - 

@article{
author = "Richter, Stefan and Lönnecke, Peter and Bovan, Dijana and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Kaluđerović, Goran N. and Hey-Hawkins, Evamarie",
year = "2023",
abstract = "The coordination behavior of three ligand precursors 2-[(2-pyridinylmethyl)amino]acetic acid hydrochloride, 4-[(2-pyridinylmethyl)amino]benzoic acid hydrochloride and 4-{[2-(pyridin-2-ylmethylamino)ethylamino]methyl}benzoic acid hydrochloride, HL1∙HCl–HL3∙HCl, respectively, in copper(II) complexes is described. The complexes were characterized by elemental analysis, ESI mass spectrometry and IR spectroscopy, as well as X-ray structural analysis. The reaction of copper(II) with HL1∙HCl in methanol afforded the polymeric complex [{Cu(µ-Cl)2(MeL1-κ2N,N’)}n] (1) featuring the methyl ester of L1 (MeL1). With HL2∙HCl or HL3∙HCl, the dimeric complex [{CuCl(µ-Cl)(HL2-κ2N,N’)}2] (2) or the mononuclear complex [CuCl2(HL3-κ3N,N’,N’’)] (3) were obtained. All complexes exhibited square-pyramidal geometries. In 1, polymeric chains are formed through bridging chlorido ligands without typical hydrogen bonding interaction. Contrarily, the COOH group in 2 is participating in the formation of intermolecular hydrogen bonding forming a supramolecular structure. In 3, intermolecular hydrogen bonding (Cl…O) leads to a 1-D polymeric structure. The copper(II) complex 2 diminished viability of human 8505C, MCF-7, 518A2 and SW480 cell lines. The tumoricidal effect of 2 was realized mainly through caspase-mediated apoptosis.",
publisher = "Belgrade: Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Square-pyramidal mononuclear, dinuclear and polymeric copper(II) complexes with (2-pyridinylmethyl)amino derivatives",
doi = "10.2298/JSC230818072R"
}

Richter, S., Lönnecke, P., Bovan, D., Mijatović, S., Maksimović-Ivanić, D., Kaluđerović, G. N.,& Hey-Hawkins, E.. (2023). Square-pyramidal mononuclear, dinuclear and polymeric copper(II) complexes with (2-pyridinylmethyl)amino derivatives. in Journal of the Serbian Chemical Society
Belgrade: Serbian Chemical Society..
https://doi.org/10.2298/JSC230818072R

Richter S, Lönnecke P, Bovan D, Mijatović S, Maksimović-Ivanić D, Kaluđerović GN, Hey-Hawkins E. Square-pyramidal mononuclear, dinuclear and polymeric copper(II) complexes with (2-pyridinylmethyl)amino derivatives. in Journal of the Serbian Chemical Society. 2023;.
doi:10.2298/JSC230818072R .

Richter, Stefan, Lönnecke, Peter, Bovan, Dijana, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Kaluđerović, Goran N., Hey-Hawkins, Evamarie, "Square-pyramidal mononuclear, dinuclear and polymeric copper(II) complexes with (2-pyridinylmethyl)amino derivatives" in Journal of the Serbian Chemical Society (2023),
https://doi.org/10.2298/JSC230818072R . .

TY  - CONF
AU  - Krajnović, Tamara
AU  - Bovan, Dijana
AU  - Vuković, Nenad L.
AU  - Vukić, Milena D.
AU  - Mihajlović, Sanja
AU  - Tanić, Nikola
AU  - Arsenijević, Nebojša
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6237
AB  - Shikonin is a naphthoquinone found in the roots of plants of the Boraginaceae family and
is widely known for its numerous biological activities, including anticancer. In this study,
the antitumor mode of action of shikonin derivatives isolated from the roots of Onosma
visianii was investigated in mouse melanoma cell line B16. MTT and CV assays showed
that six examined shikonins decreased B16 cell viability in a dose-dependent manner, with
compounds 5 and 6 exhibiting the highest cytotoxic activity. This effect correlated with
caspase-mediated apoptosis, which was detected by flow cytometry and fluorescence
microscopy. In addition, CFSE staining revealed a strong blockage of cell division in
response to treatment, with a more profound effect of compound 6. The altered cell
morphology together with the loss of dividing potential upon exposure to both shikonins
implied reprogramming of the B16 cell phenotype. The absence of melanogenesis
enhancement coupled with an elevated level of myelin basic protein in response to
treatment with both tested agents suggested that the cells transdifferentiated into a
Schwann-like phenotype, with possible involvement of the autophagic process in this
conversion. Differentiation of malignant cells has become favourable in cancer treatment,
bearing in mind the phenomenon of apoptosis-induced proliferation. Hence, the specific
antitumor mode of action of shikonin derivatives on melanoma in vitro shown here
provides a good platform for new investigations of these promising natural compounds.
PB  - Belgrade: Faculty of Chemistry
C3  - Biochemistry in Biotechnology": Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
T1  - Shikonin derivatives trigger phenotype reprogramming of B16 mouse melanoma cells
SP  - 96
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6237
ER  - 

@conference{
author = "Krajnović, Tamara and Bovan, Dijana and Vuković, Nenad L. and Vukić, Milena D. and Mihajlović, Sanja and Tanić, Nikola and Arsenijević, Nebojša and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Shikonin is a naphthoquinone found in the roots of plants of the Boraginaceae family and
is widely known for its numerous biological activities, including anticancer. In this study,
the antitumor mode of action of shikonin derivatives isolated from the roots of Onosma
visianii was investigated in mouse melanoma cell line B16. MTT and CV assays showed
that six examined shikonins decreased B16 cell viability in a dose-dependent manner, with
compounds 5 and 6 exhibiting the highest cytotoxic activity. This effect correlated with
caspase-mediated apoptosis, which was detected by flow cytometry and fluorescence
microscopy. In addition, CFSE staining revealed a strong blockage of cell division in
response to treatment, with a more profound effect of compound 6. The altered cell
morphology together with the loss of dividing potential upon exposure to both shikonins
implied reprogramming of the B16 cell phenotype. The absence of melanogenesis
enhancement coupled with an elevated level of myelin basic protein in response to
treatment with both tested agents suggested that the cells transdifferentiated into a
Schwann-like phenotype, with possible involvement of the autophagic process in this
conversion. Differentiation of malignant cells has become favourable in cancer treatment,
bearing in mind the phenomenon of apoptosis-induced proliferation. Hence, the specific
antitumor mode of action of shikonin derivatives on melanoma in vitro shown here
provides a good platform for new investigations of these promising natural compounds.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Biochemistry in Biotechnology": Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia",
title = "Shikonin derivatives trigger phenotype reprogramming of B16 mouse melanoma cells",
pages = "96",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6237"
}

Krajnović, T., Bovan, D., Vuković, N. L., Vukić, M. D., Mihajlović, S., Tanić, N., Arsenijević, N.,& Maksimović-Ivanić, D.. (2023). Shikonin derivatives trigger phenotype reprogramming of B16 mouse melanoma cells. in Biochemistry in Biotechnology": Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
Belgrade: Faculty of Chemistry., 96.
https://hdl.handle.net/21.15107/rcub_ibiss_6237

Krajnović T, Bovan D, Vuković NL, Vukić MD, Mihajlović S, Tanić N, Arsenijević N, Maksimović-Ivanić D. Shikonin derivatives trigger phenotype reprogramming of B16 mouse melanoma cells. in Biochemistry in Biotechnology": Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia. 2023;:96.
https://hdl.handle.net/21.15107/rcub_ibiss_6237 .

Krajnović, Tamara, Bovan, Dijana, Vuković, Nenad L., Vukić, Milena D., Mihajlović, Sanja, Tanić, Nikola, Arsenijević, Nebojša, Maksimović-Ivanić, Danijela, "Shikonin derivatives trigger phenotype reprogramming of B16 mouse melanoma cells" in Biochemistry in Biotechnology": Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia (2023):96,
https://hdl.handle.net/21.15107/rcub_ibiss_6237 .

TY  - CONF
AU  - Komazec, Teodora
AU  - Mihajlović, Ekatarina
AU  - Bovan, Dijana
AU  - Mijatović, Sanja
AU  - Predarska, Ivana
AU  - Hey-Hawkins, Evamarie
AU  - Kaluđerović, Goran N.
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - https://www.sdir.ac.rs/oncology-insights/
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6215
AB  - Background: Active contribution of cyclooxygenase enzymes (COX) and their products, in particular prostaglandin E2, to tumor progression makes this enzyme an attractive target for molecular therapy in cancer. The combination of conventional chemotherapeutic drugs with COX1/2 inhibitors, and further enhancement of their delivery into target tissue can be a highly prospective approach in cancer therapy, especially in advanced stages. Accordingly, a cytostatic and anti-inflammatory drug conjugate was synthesised, as well as its immobilization in mesoporous nanostructured silica SBA-15. Detailed evaluation of the cytotoxic potential and the mechanism of action of this conjugate and the appropriate material on B16 cells was further performed in vitro and in vivo. Material and Methods: Cell viability of B16 melanoma cells was determined by MTT and CV assays. Cell morphology was estimated by hematoxylin–eosin and Oil Red O staining using light microscopy, while changes in the nuclei were validated by PI staining using fluorescent microscopy. Differentiation of melanoma cells was determined by measurement of tyrosinase activity and the presence of melanin. Syngeneic C57BL/6 mice model was used for in vivo assessment of the tumorigenic potential of B16 cells exposed to free and SBA-15 loaded conjugate in vitro, as well as for the evaluation of the antitumor potential of the experimental substances given in the therapeutic regimen. Results and Conclusion: Exposure to free or immobilized cisplatin-ibuprofen conjugate decreased the viability of the B16 cell culture while morphology of survived cells was changed. Cytoplasm of enlarged and elongated cells showed intensive granularity with enhanced lipid content and huge irregularly shaped nuclei with prominent heterochromatin foci, all of which indicated senescent state. Increased activity of tyrosinase and the presence of melanin compared to the control, referred to the differentiation of melanoma cells toward primary phenotype. Further inoculation of pretreated B16 cells into C57BL/6 mice showed decreased potential to form tumor in comparison to tumorigenic potential of untreated cells. Additionally, in vivo application of free and SBA-15 immobilized conjugate in therapeutic regiment led to statistically significant reduction of tumor volume, with only fewer signs of toxicity compared to cisplatin as positive control. New knowledge about this compound and corresponding material is reflected in their antitumor potential on mouse melanoma cells, which opens numerous possibilities for further research.
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 effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo
SP  - 62
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6215
ER  - 

@conference{
author = "Komazec, Teodora and Mihajlović, Ekatarina and Bovan, Dijana and Mijatović, Sanja and Predarska, Ivana and Hey-Hawkins, Evamarie and Kaluđerović, Goran N. and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Background: Active contribution of cyclooxygenase enzymes (COX) and their products, in particular prostaglandin E2, to tumor progression makes this enzyme an attractive target for molecular therapy in cancer. The combination of conventional chemotherapeutic drugs with COX1/2 inhibitors, and further enhancement of their delivery into target tissue can be a highly prospective approach in cancer therapy, especially in advanced stages. Accordingly, a cytostatic and anti-inflammatory drug conjugate was synthesised, as well as its immobilization in mesoporous nanostructured silica SBA-15. Detailed evaluation of the cytotoxic potential and the mechanism of action of this conjugate and the appropriate material on B16 cells was further performed in vitro and in vivo. Material and Methods: Cell viability of B16 melanoma cells was determined by MTT and CV assays. Cell morphology was estimated by hematoxylin–eosin and Oil Red O staining using light microscopy, while changes in the nuclei were validated by PI staining using fluorescent microscopy. Differentiation of melanoma cells was determined by measurement of tyrosinase activity and the presence of melanin. Syngeneic C57BL/6 mice model was used for in vivo assessment of the tumorigenic potential of B16 cells exposed to free and SBA-15 loaded conjugate in vitro, as well as for the evaluation of the antitumor potential of the experimental substances given in the therapeutic regimen. Results and Conclusion: Exposure to free or immobilized cisplatin-ibuprofen conjugate decreased the viability of the B16 cell culture while morphology of survived cells was changed. Cytoplasm of enlarged and elongated cells showed intensive granularity with enhanced lipid content and huge irregularly shaped nuclei with prominent heterochromatin foci, all of which indicated senescent state. Increased activity of tyrosinase and the presence of melanin compared to the control, referred to the differentiation of melanoma cells toward primary phenotype. Further inoculation of pretreated B16 cells into C57BL/6 mice showed decreased potential to form tumor in comparison to tumorigenic potential of untreated cells. Additionally, in vivo application of free and SBA-15 immobilized conjugate in therapeutic regiment led to statistically significant reduction of tumor volume, with only fewer signs of toxicity compared to cisplatin as positive control. New knowledge about this compound and corresponding material is reflected in their antitumor potential on mouse melanoma cells, which opens numerous possibilities for further research.",
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 effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo",
pages = "62",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6215"
}

Komazec, T., Mihajlović, E., Bovan, D., Mijatović, S., Predarska, I., Hey-Hawkins, E., Kaluđerović, G. N.,& Maksimović-Ivanić, D.. (2023). The effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo. 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., 62.
https://hdl.handle.net/21.15107/rcub_ibiss_6215

Komazec T, Mihajlović E, Bovan D, Mijatović S, Predarska I, Hey-Hawkins E, Kaluđerović GN, Maksimović-Ivanić D. The effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo. 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;:62.
https://hdl.handle.net/21.15107/rcub_ibiss_6215 .

Komazec, Teodora, Mihajlović, Ekatarina, Bovan, Dijana, Mijatović, Sanja, Predarska, Ivana, Hey-Hawkins, Evamarie, Kaluđerović, Goran N., Maksimović-Ivanić, Danijela, "The effects of cisplatin-ibuprofen conjugate free and immobilized in mesoporous nanostructured silica on the change of morphology of mouse melanoma cells, and antitumor potential in vivo" 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):62,
https://hdl.handle.net/21.15107/rcub_ibiss_6215 .

TY  - CONF
AU  - Komazec, Teodora
AU  - Mihajlović, Ekatarina
AU  - Bovan, Dijana
AU  - Mijatović, Sanja
AU  - Predarska, Ivana
AU  - Kaluđerović, Goran N.
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6217
AB  - Overexpression of cyclooxygenase (COX) and thus, prostaglandin E2 in numerous cancers
justified COX inhibitors testing in cancer prevention or treatment 1. Conjugate molecules of
COX inhibitors and common chemotherapeutic drugs, as well as their immobilization in
nanoparticles that increases drug delivery and accumulation in tumor tissue, can potentially
improve approaches in cancer therapy. Cisplatin-naproxen conjugate and corresponding
SBA-15 counterpart decreased the viability of B16 cells. Enlarged and elongated cells with
distinctly granular cytoplasm and the increased presence of lipid droplets were noticed
after haematoxylin–eosin and Oil Red O staining of treated cultures. In addition, enormous
nuclei and markedly heterochromatin foci were confirmed by PI staining indicating
establishment of senescent state upon the treatment. Alongside, differentiation of
melanoma cells toward melanocytes was demonstrated by elevated tyrosinase activity and
presence of melanin, thus leading to reduced tumorigenic potential in vivo. In addition,
cisplatin-naproxen conjugate and corresponding SBA-15 counterpart significantly reduced
melanoma growth in C57BL/6 mice, with lesser signs of toxicity compared to cisplatin as
a positive control. Strong antitumor potential of both, free and immobilized conjugates on
mouse melanoma cells opens numerous possibilities for further research.
PB  - Belgrade: Faculty of Chemistry
C3  - Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
T1  - Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model
SP  - 97
EP  - 98
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6217
ER  - 

@conference{
author = "Komazec, Teodora and Mihajlović, Ekatarina and Bovan, Dijana and Mijatović, Sanja and Predarska, Ivana and Kaluđerović, Goran N. and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2023",
abstract = "Overexpression of cyclooxygenase (COX) and thus, prostaglandin E2 in numerous cancers
justified COX inhibitors testing in cancer prevention or treatment 1. Conjugate molecules of
COX inhibitors and common chemotherapeutic drugs, as well as their immobilization in
nanoparticles that increases drug delivery and accumulation in tumor tissue, can potentially
improve approaches in cancer therapy. Cisplatin-naproxen conjugate and corresponding
SBA-15 counterpart decreased the viability of B16 cells. Enlarged and elongated cells with
distinctly granular cytoplasm and the increased presence of lipid droplets were noticed
after haematoxylin–eosin and Oil Red O staining of treated cultures. In addition, enormous
nuclei and markedly heterochromatin foci were confirmed by PI staining indicating
establishment of senescent state upon the treatment. Alongside, differentiation of
melanoma cells toward melanocytes was demonstrated by elevated tyrosinase activity and
presence of melanin, thus leading to reduced tumorigenic potential in vivo. In addition,
cisplatin-naproxen conjugate and corresponding SBA-15 counterpart significantly reduced
melanoma growth in C57BL/6 mice, with lesser signs of toxicity compared to cisplatin as
a positive control. Strong antitumor potential of both, free and immobilized conjugates on
mouse melanoma cells opens numerous possibilities for further research.",
publisher = "Belgrade: Faculty of Chemistry",
journal = "Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia",
title = "Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model",
pages = "97-98",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6217"
}

Komazec, T., Mihajlović, E., Bovan, D., Mijatović, S., Predarska, I., Kaluđerović, G. N., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2023). Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia
Belgrade: Faculty of Chemistry., 97-98.
https://hdl.handle.net/21.15107/rcub_ibiss_6217

Komazec T, Mihajlović E, Bovan D, Mijatović S, Predarska I, Kaluđerović GN, Hey-Hawkins E, Maksimović-Ivanić D. Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model. in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia. 2023;:97-98.
https://hdl.handle.net/21.15107/rcub_ibiss_6217 .

Komazec, Teodora, Mihajlović, Ekatarina, Bovan, Dijana, Mijatović, Sanja, Predarska, Ivana, Kaluđerović, Goran N., Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Cisplatin-naproxen conjugate free and loaded in SBA- 15 indicate morphological changes and antitumor activity in vivo in mouse melanoma model" in Biochemistry in Biotechnology: Serbian Biochemical Society, Twelfth Conference, International scientific meeting; 2023 Sep 21-23; Belgrade, Serbia (2023):97-98,
https://hdl.handle.net/21.15107/rcub_ibiss_6217 .

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  - Li, Hanluo
AU  - Ziemer, Mirjana
AU  - Stojanović, Ivana D.
AU  - Saksida, Tamara
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Đmura, Goran
AU  - Mićanović, Dragica
AU  - Koprivica, Ivan
AU  - Krajnović, Tamara
AU  - Drača, Dijana
AU  - Simon, Jan-Christoph
AU  - Lethaus, Bernd
AU  - Savković, Vuk
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4775
AB  - Wound  healing  of  acute  full-thickness  injuries  and  chronic  non-healing  ulcers  leads  to  delayed  wound  closure,  prolonged recovery period and hypertrophic scarring, generating a demand for an autologous cell therapy and a relevant pre-clinical research  models for  wound healing.  In this study, an  immunocompetent model  for  wound  healing  was  employed  using a syngeneic murine cell line of mesenchymal stem cells cultured from the mouse whisker hair follicle outer root sheath (named moMSCORS). moMSCORS were isolated using an air-liquid interface method, expanded  in vitro  and characterized according to the MSC definition criteria - cell viability,  in vitro  proliferation, MSC phenotype and multi-lineage differentiations. Moreover, upon applying moMSCORS in an  in vivo  full-thickness wound model in the syngeneic C57BL/6 mice, the treated wounds displayed different morphology to that of the untreated wound beds. Quantitative evaluation of angiogenesis, granulation and wound closure involving clinical scoring and software-based quantification indicated a lower degree of inflammation in the treated wounds. Histological staining of treated wounds by the means of H&E, Alcian Blue, PicroSirius Red and αSMA immune labelling showed lower cellularity, less collagen filaments as well as thinner dermal and epidermal layers compared with the untreated wounds, indicating a general reduction of hypertrophic scars. The decreased inflammation, accelerated wound closure and non-hypertrophic scarring, which were facilitated by moMSCORS, hereby address a common problem of hypertrophic scars and non-physiological tissue properties upon wound closure, and additionally offer an  in  vivo  model  for  the  autologous  cell-based  wound  healing.
PB  - Basel: Springer Nature Switzerland AG
T2  - Stem Cell Reviews and Reports
T1  - Mesenchymal Stem Cells From Mouse Hair Follicles Reduce Hypertrophic Scarring in a Murine  Wound Healing Model
DO  - 10.1007/s12015-021-10288-7
ER  - 

@article{
author = "Li, Hanluo and Ziemer, Mirjana and Stojanović, Ivana D. and Saksida, Tamara and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Đmura, Goran and Mićanović, Dragica and Koprivica, Ivan and Krajnović, Tamara and Drača, Dijana and Simon, Jan-Christoph and Lethaus, Bernd and Savković, Vuk",
year = "2022",
abstract = "Wound  healing  of  acute  full-thickness  injuries  and  chronic  non-healing  ulcers  leads  to  delayed  wound  closure,  prolonged recovery period and hypertrophic scarring, generating a demand for an autologous cell therapy and a relevant pre-clinical research  models for  wound healing.  In this study, an  immunocompetent model  for  wound  healing  was  employed  using a syngeneic murine cell line of mesenchymal stem cells cultured from the mouse whisker hair follicle outer root sheath (named moMSCORS). moMSCORS were isolated using an air-liquid interface method, expanded  in vitro  and characterized according to the MSC definition criteria - cell viability,  in vitro  proliferation, MSC phenotype and multi-lineage differentiations. Moreover, upon applying moMSCORS in an  in vivo  full-thickness wound model in the syngeneic C57BL/6 mice, the treated wounds displayed different morphology to that of the untreated wound beds. Quantitative evaluation of angiogenesis, granulation and wound closure involving clinical scoring and software-based quantification indicated a lower degree of inflammation in the treated wounds. Histological staining of treated wounds by the means of H&E, Alcian Blue, PicroSirius Red and αSMA immune labelling showed lower cellularity, less collagen filaments as well as thinner dermal and epidermal layers compared with the untreated wounds, indicating a general reduction of hypertrophic scars. The decreased inflammation, accelerated wound closure and non-hypertrophic scarring, which were facilitated by moMSCORS, hereby address a common problem of hypertrophic scars and non-physiological tissue properties upon wound closure, and additionally offer an  in  vivo  model  for  the  autologous  cell-based  wound  healing.",
publisher = "Basel: Springer Nature Switzerland AG",
journal = "Stem Cell Reviews and Reports",
title = "Mesenchymal Stem Cells From Mouse Hair Follicles Reduce Hypertrophic Scarring in a Murine  Wound Healing Model",
doi = "10.1007/s12015-021-10288-7"
}

Li, H., Ziemer, M., Stojanović, I. D., Saksida, T., Maksimović-Ivanić, D., Mijatović, S., Đmura, G., Mićanović, D., Koprivica, I., Krajnović, T., Drača, D., Simon, J., Lethaus, B.,& Savković, V.. (2022). Mesenchymal Stem Cells From Mouse Hair Follicles Reduce Hypertrophic Scarring in a Murine  Wound Healing Model. in Stem Cell Reviews and Reports
Basel: Springer Nature Switzerland AG..
https://doi.org/10.1007/s12015-021-10288-7

Li H, Ziemer M, Stojanović ID, Saksida T, Maksimović-Ivanić D, Mijatović S, Đmura G, Mićanović D, Koprivica I, Krajnović T, Drača D, Simon J, Lethaus B, Savković V. Mesenchymal Stem Cells From Mouse Hair Follicles Reduce Hypertrophic Scarring in a Murine  Wound Healing Model. in Stem Cell Reviews and Reports. 2022;.
doi:10.1007/s12015-021-10288-7 .

Li, Hanluo, Ziemer, Mirjana, Stojanović, Ivana D., Saksida, Tamara, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Đmura, Goran, Mićanović, Dragica, Koprivica, Ivan, Krajnović, Tamara, Drača, Dijana, Simon, Jan-Christoph, Lethaus, Bernd, Savković, Vuk, "Mesenchymal Stem Cells From Mouse Hair Follicles Reduce Hypertrophic Scarring in a Murine  Wound Healing Model" in Stem Cell Reviews and Reports (2022),
https://doi.org/10.1007/s12015-021-10288-7 . .

TY  - JOUR
AU  - Predarska, Ivana
AU  - Saoud, Mohamad
AU  - Drača, Dijana
AU  - Morgan, Ibrahim
AU  - Komazec, Teodora
AU  - Eichhorn, Thomas
AU  - Mihajlović, Ekatarina
AU  - Dunđerović, Duško
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
AU  - Kaluđerović, Goran N.
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5238
AB  - The main reasons for the limited clinical efficacy of the platinum(II)-based agent cisplatin
include drug resistance and significant side effects. Due to their better stability, as well as the
possibility to introduce biologically active ligands in their axial positions constructing multifunctional
prodrugs, creating platinum(IV) complexes is a tempting strategy for addressing these limitations.
Another strategy for developing chemotherapeutics with lower toxicity relies on the ability of
nanoparticles to accumulate in greater quantities in tumor tissues through passive targeting. To
combine the two approaches, three platinum(IV) conjugates based on a cisplatin scaffold containing
in the axial positions derivatives of caffeic and ferulic acid were prepared and loaded into SBA-
15 to produce the corresponding mesoporous silica nanoparticles (MSNs). The free platinum(IV)
conjugates demonstrated higher or comparable activity with respect to cisplatin against different
human breast cancer cell lines, while upon immobilization, superior antiproliferative activity with
markedly increased cytotoxicity (more than 1000-fold lower IC50 values) compared to cisplatin was
observed. Mechanistic investigations with the most potent conjugate, cisplatin-diacetyl caffeate (1),
and the corresponding MSNs (SBA-15|1) in a 4T1 mouse breast cancer cell line showed that these
compounds induce apoptotic cell death causing strong caspase activation. In vivo, in BALB/c mice,
1 and SBA-15|1 inhibited the tumor growth while decreasing the necrotic area and lowering the
mitotic rate.
PB  - Basel: MDPI
T2  - Nanomaterials
T1  - Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines
IS  - 21
VL  - 12
DO  - 10.3390/nano12213767
SP  - 3767
ER  - 

@article{
author = "Predarska, Ivana and Saoud, Mohamad and Drača, Dijana and Morgan, Ibrahim and Komazec, Teodora and Eichhorn, Thomas and Mihajlović, Ekatarina and Dunđerović, Duško and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie and Kaluđerović, Goran N.",
year = "2022",
abstract = "The main reasons for the limited clinical efficacy of the platinum(II)-based agent cisplatin
include drug resistance and significant side effects. Due to their better stability, as well as the
possibility to introduce biologically active ligands in their axial positions constructing multifunctional
prodrugs, creating platinum(IV) complexes is a tempting strategy for addressing these limitations.
Another strategy for developing chemotherapeutics with lower toxicity relies on the ability of
nanoparticles to accumulate in greater quantities in tumor tissues through passive targeting. To
combine the two approaches, three platinum(IV) conjugates based on a cisplatin scaffold containing
in the axial positions derivatives of caffeic and ferulic acid were prepared and loaded into SBA-
15 to produce the corresponding mesoporous silica nanoparticles (MSNs). The free platinum(IV)
conjugates demonstrated higher or comparable activity with respect to cisplatin against different
human breast cancer cell lines, while upon immobilization, superior antiproliferative activity with
markedly increased cytotoxicity (more than 1000-fold lower IC50 values) compared to cisplatin was
observed. Mechanistic investigations with the most potent conjugate, cisplatin-diacetyl caffeate (1),
and the corresponding MSNs (SBA-15|1) in a 4T1 mouse breast cancer cell line showed that these
compounds induce apoptotic cell death causing strong caspase activation. In vivo, in BALB/c mice,
1 and SBA-15|1 inhibited the tumor growth while decreasing the necrotic area and lowering the
mitotic rate.",
publisher = "Basel: MDPI",
journal = "Nanomaterials",
title = "Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines",
number = "21",
volume = "12",
doi = "10.3390/nano12213767",
pages = "3767"
}

Predarska, I., Saoud, M., Drača, D., Morgan, I., Komazec, T., Eichhorn, T., Mihajlović, E., Dunđerović, D., Mijatović, S., Maksimović-Ivanić, D., Hey-Hawkins, E.,& Kaluđerović, G. N.. (2022). Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines. in Nanomaterials
Basel: MDPI., 12(21), 3767.
https://doi.org/10.3390/nano12213767

Predarska I, Saoud M, Drača D, Morgan I, Komazec T, Eichhorn T, Mihajlović E, Dunđerović D, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E, Kaluđerović GN. Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines. in Nanomaterials. 2022;12(21):3767.
doi:10.3390/nano12213767 .

Predarska, Ivana, Saoud, Mohamad, Drača, Dijana, Morgan, Ibrahim, Komazec, Teodora, Eichhorn, Thomas, Mihajlović, Ekatarina, Dunđerović, Duško, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, Kaluđerović, Goran N., "Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines" in Nanomaterials, 12, no. 21 (2022):3767,
https://doi.org/10.3390/nano12213767 . .

TY  - JOUR
AU  - Markelić, Milica
AU  - Drača, Dijana
AU  - Krajnović, Tamara
AU  - Jović, Zorana
AU  - Vuksanović, Milica
AU  - Koruga, Djuro
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4953
AB  - (1) Background: Their unique structure and electron deficiency have brought fullerenes
into the focus of research in many fields, including medicine. The hyper-harmonized hydroxylated
fullerene water complex (3HFWC) formulation has solved the limitations of the poor solubility
and bioavailability of fullerenes. To achieve better antitumor activity, 3HFWC was combined with
short-term irradiation of cells with hyperpolarized light (HPL) generated by the application of a
nanophotonic fullerene filter in a Bioptron® device. The benefits of HPL were confirmed in the
microcirculation, wound healing and immunological function. (2) Methods: B16, B16-F10 and A375
melanoma cells were exposed to a wide spectrum of 3HFWC doses and to a single short-term HPL
irradiation. (3) Results: Apart from the differences in the redox status and level of invasiveness, the
effects of the treatments were quite similar. Decreased viability, morphological alteration, signs of
melanocytic differentiation and cellular senescence were observed upon the successful internalization
of the nanoquantum substance. (4) Conclusions: Overall, 3HFWC/HPL promoted melanoma cell
reprogramming toward a normal phenotype.
PB  - Basel: MDPI
T2  - Nanomaterials (Basel)
T1  - Combined Action of Hyper-Harmonized Hydroxylated Fullerene Water Complex and Hyperpolarized Light Leads to Melanoma Cell Reprogramming In Vitro
IS  - 8
VL  - 12
DO  - 10.3390/nano12081331
SP  - 1331
ER  - 

@article{
author = "Markelić, Milica and Drača, Dijana and Krajnović, Tamara and Jović, Zorana and Vuksanović, Milica and Koruga, Djuro and Mijatović, Sanja and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "(1) Background: Their unique structure and electron deficiency have brought fullerenes
into the focus of research in many fields, including medicine. The hyper-harmonized hydroxylated
fullerene water complex (3HFWC) formulation has solved the limitations of the poor solubility
and bioavailability of fullerenes. To achieve better antitumor activity, 3HFWC was combined with
short-term irradiation of cells with hyperpolarized light (HPL) generated by the application of a
nanophotonic fullerene filter in a Bioptron® device. The benefits of HPL were confirmed in the
microcirculation, wound healing and immunological function. (2) Methods: B16, B16-F10 and A375
melanoma cells were exposed to a wide spectrum of 3HFWC doses and to a single short-term HPL
irradiation. (3) Results: Apart from the differences in the redox status and level of invasiveness, the
effects of the treatments were quite similar. Decreased viability, morphological alteration, signs of
melanocytic differentiation and cellular senescence were observed upon the successful internalization
of the nanoquantum substance. (4) Conclusions: Overall, 3HFWC/HPL promoted melanoma cell
reprogramming toward a normal phenotype.",
publisher = "Basel: MDPI",
journal = "Nanomaterials (Basel)",
title = "Combined Action of Hyper-Harmonized Hydroxylated Fullerene Water Complex and Hyperpolarized Light Leads to Melanoma Cell Reprogramming In Vitro",
number = "8",
volume = "12",
doi = "10.3390/nano12081331",
pages = "1331"
}

Markelić, M., Drača, D., Krajnović, T., Jović, Z., Vuksanović, M., Koruga, D., Mijatović, S.,& Maksimović-Ivanić, D.. (2022). Combined Action of Hyper-Harmonized Hydroxylated Fullerene Water Complex and Hyperpolarized Light Leads to Melanoma Cell Reprogramming In Vitro. in Nanomaterials (Basel)
Basel: MDPI., 12(8), 1331.
https://doi.org/10.3390/nano12081331

Markelić M, Drača D, Krajnović T, Jović Z, Vuksanović M, Koruga D, Mijatović S, Maksimović-Ivanić D. Combined Action of Hyper-Harmonized Hydroxylated Fullerene Water Complex and Hyperpolarized Light Leads to Melanoma Cell Reprogramming In Vitro. in Nanomaterials (Basel). 2022;12(8):1331.
doi:10.3390/nano12081331 .

Markelić, Milica, Drača, Dijana, Krajnović, Tamara, Jović, Zorana, Vuksanović, Milica, Koruga, Djuro, Mijatović, Sanja, Maksimović-Ivanić, Danijela, "Combined Action of Hyper-Harmonized Hydroxylated Fullerene Water Complex and Hyperpolarized Light Leads to Melanoma Cell Reprogramming In Vitro" in Nanomaterials (Basel), 12, no. 8 (2022):1331,
https://doi.org/10.3390/nano12081331 . .

TY  - JOUR
AU  - Kuhnert, Robert
AU  - Kuhnert, Lydia
AU  - Sárosi, Menyhárt‐B.
AU  - George, Sven
AU  - Drača, Dijana
AU  - Paskaš, Svetlana
AU  - Hofmann, Bettina
AU  - Steinhilber, Dieter
AU  - Honscha, Walther
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
PY  - 2022
UR  - https://onlinelibrary.wiley.com/doi/10.1002/cmdc.202100588
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4686
AB  - 12-Lipoxygenase is crucial for tumour angiogenesis. 5,6,7-Trihydroxy-2-phenyl-4H-1-benzopyran-4-one (baicalein) is a suitable inhibitor for this enzyme but is rapidly metabolised in vivo. Thus, an improvement of the metabolic stability is necessary to enhance the therapeutic efficiency. An emerging approach to enhance metabolic stability of carbon-based pharmaceuticals is the use of metabolically stable, non-toxic boron clusters, such as dicarba-closo-dodecaborane(12)s (carboranes) as phenyl mimetics. Therefore, the unsubstituted phenyl ring of baicalein was replaced by meta-carborane, resulting in borcalein, the carborane analogue of baicalein. This substitution resulted in a decreased inhibitory activity toward 12-lipoxygenase, but led to increased toxicity in melanoma (A375, B16, B16F10) and colon cancer cell lines (SW480, HCT116, CT26CL25) with decreased tumour selectivity in comparison to baicalein. Surprisingly, borcalein displays a different mechanism of cytotoxicity with increased intracellular production of reactive oxygen species (ROS), reactive nitrogen species (RNS) and nitric oxide (NO).
PB  - Weinheim: John Wiley and Sons Ltd.
T2  - ChemMedChem
T1  - Borcalein: a Carborane-Based Analogue of Baicalein with 12-Lipoxygenase-Independent Toxicity
IS  - 1
VL  - 17
DO  - 10.1002/cmdc.202100588
SP  - e202100588
ER  - 

@article{
author = "Kuhnert, Robert and Kuhnert, Lydia and Sárosi, Menyhárt‐B. and George, Sven and Drača, Dijana and Paskaš, Svetlana and Hofmann, Bettina and Steinhilber, Dieter and Honscha, Walther and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie",
year = "2022",
abstract = "12-Lipoxygenase is crucial for tumour angiogenesis. 5,6,7-Trihydroxy-2-phenyl-4H-1-benzopyran-4-one (baicalein) is a suitable inhibitor for this enzyme but is rapidly metabolised in vivo. Thus, an improvement of the metabolic stability is necessary to enhance the therapeutic efficiency. An emerging approach to enhance metabolic stability of carbon-based pharmaceuticals is the use of metabolically stable, non-toxic boron clusters, such as dicarba-closo-dodecaborane(12)s (carboranes) as phenyl mimetics. Therefore, the unsubstituted phenyl ring of baicalein was replaced by meta-carborane, resulting in borcalein, the carborane analogue of baicalein. This substitution resulted in a decreased inhibitory activity toward 12-lipoxygenase, but led to increased toxicity in melanoma (A375, B16, B16F10) and colon cancer cell lines (SW480, HCT116, CT26CL25) with decreased tumour selectivity in comparison to baicalein. Surprisingly, borcalein displays a different mechanism of cytotoxicity with increased intracellular production of reactive oxygen species (ROS), reactive nitrogen species (RNS) and nitric oxide (NO).",
publisher = "Weinheim: John Wiley and Sons Ltd.",
journal = "ChemMedChem",
title = "Borcalein: a Carborane-Based Analogue of Baicalein with 12-Lipoxygenase-Independent Toxicity",
number = "1",
volume = "17",
doi = "10.1002/cmdc.202100588",
pages = "e202100588"
}

Kuhnert, R., Kuhnert, L., Sárosi, Menyhárt‐B., George, S., Drača, D., Paskaš, S., Hofmann, B., Steinhilber, D., Honscha, W., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2022). Borcalein: a Carborane-Based Analogue of Baicalein with 12-Lipoxygenase-Independent Toxicity. in ChemMedChem
Weinheim: John Wiley and Sons Ltd.., 17(1), e202100588.
https://doi.org/10.1002/cmdc.202100588

Kuhnert R, Kuhnert L, Sárosi M, George S, Drača D, Paskaš S, Hofmann B, Steinhilber D, Honscha W, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Borcalein: a Carborane-Based Analogue of Baicalein with 12-Lipoxygenase-Independent Toxicity. in ChemMedChem. 2022;17(1):e202100588.
doi:10.1002/cmdc.202100588 .

Kuhnert, Robert, Kuhnert, Lydia, Sárosi, Menyhárt‐B., George, Sven, Drača, Dijana, Paskaš, Svetlana, Hofmann, Bettina, Steinhilber, Dieter, Honscha, Walther, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Borcalein: a Carborane-Based Analogue of Baicalein with 12-Lipoxygenase-Independent Toxicity" in ChemMedChem, 17, no. 1 (2022):e202100588,
https://doi.org/10.1002/cmdc.202100588 . .

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  - Drača, Dijana
AU  - Mijatović, Sanja
AU  - Krajnović, Tamara
AU  - Bogdanović Pristov, Jelena
AU  - Đukić, Tatjana
AU  - Kaluđerović, Goran N.
AU  - Wessjohann, Ludger A.
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5292
AB  - Tubulisins are natural peptide compounds isolated from mycobacterial genera.
They belong to the group of antimitotic agents, since they achieve their antitumor
effect disrupting the function of mitotic spindle. The object of this study was to investigate
anticancer potential of synthetic analogue of tubulysins, tubugi 1, on mouse
melanoma model, in vitro and in vivo. Tubugi 1 decreased dose-dependently viability
of B16 cells. The experimental compound induced atypical apoptosis without the externalization
of phosphatidylserines (PS). Although apoptosis was accompanied with
strong intracellular production of reactive oxygen and nitrogen species, decrease in
malonyldyaldehyde content showed that membrane lipids were not subjected to oxidation,
what is a prerequisite for the externalization of PS. Although PS plays a key
role in the removal of apoptotic cells, this did not affect the phagocytic activity of
macrophages in vitro, implying PS-independent apoptotic cells removal. The effect of
the experimental agent was confirmed in vivo. Мacrophages isolated from peritoneal
exudate of treated animals showed cytotoxic activity, what was in line with demonstrated
expression of M1 phenotype markers, as well as production of nitric oxide.
Additonally, the phagocytic activity of these cells was preserved. Having in mind lack
of data in the literature concerning the effects of this group of agents on components
of the innate immune system, tubugi 1 remains worthy of further research in the field
of experimental oncology.
AB  - Тубулизини су природна једињења изолована из родова миксобактерија.
Спадају у групу антимитотских агенаса будући да свој антитуморски ефекат
остварују на нивоу деобног вретена. У овој студији испитиван је антитумор-
ски потенцијал синтетског аналога тубулизина, тубуги 1, in vitro и in vivo на
моделу мишјег меланома. Тубуги 1 је на дозно-зависан начин смањио вијаби-
литет B16 ћелија. Експериментално једињење је у овим ћелијама индуковало
атипичну форму апоптотске ћелијске смрти без екстернализације фосфати-
дилсерина (ПС). Иако је апоптоза била праћена снажном продукцијом ре-
активних врста кисеоника и азота, смањење садржаја малонилдиалдехида је
показало да мембрански липиди нису подлегли оксидацији, што је предуслов
за екстернализацију ПС. Иако ПС има кључну улогу у уклањању апоптотских
ћелија, ово се није одразило на фагоцитну активност макрофага in vitro, ука-
зујући на фагоцитозу независну од ПС. Учинак експерименталног агенса је
потврђен in vivo. Макрофаги изоловани из перитонеалног ексудата третира-
них животиња показали су цитотоксичну активност, што је у сагласности са
показаном експресијом маркера М1 фенотипа и продукцијом азот моноксида.
Додатно, фагоцитна способност ових ћелија је била очувана. С обзиром на
недостатак података у литератури о деловању овакве групе агенаса на компо-
ненте урођеног имунског система, тубуги 1 остаје вредан даљих испитивања
на пољу 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  - New aspects of synthetic tubulysin derivative, tubugi 1, action in murine melanoma model
SP  - 41
SP  - 42
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5292
ER  - 

@conference{
author = "Drača, Dijana and Mijatović, Sanja and Krajnović, Tamara and Bogdanović Pristov, Jelena and Đukić, Tatjana and Kaluđerović, Goran N. and Wessjohann, Ludger A. and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "Tubulisins are natural peptide compounds isolated from mycobacterial genera.
They belong to the group of antimitotic agents, since they achieve their antitumor
effect disrupting the function of mitotic spindle. The object of this study was to investigate
anticancer potential of synthetic analogue of tubulysins, tubugi 1, on mouse
melanoma model, in vitro and in vivo. Tubugi 1 decreased dose-dependently viability
of B16 cells. The experimental compound induced atypical apoptosis without the externalization
of phosphatidylserines (PS). Although apoptosis was accompanied with
strong intracellular production of reactive oxygen and nitrogen species, decrease in
malonyldyaldehyde content showed that membrane lipids were not subjected to oxidation,
what is a prerequisite for the externalization of PS. Although PS plays a key
role in the removal of apoptotic cells, this did not affect the phagocytic activity of
macrophages in vitro, implying PS-independent apoptotic cells removal. The effect of
the experimental agent was confirmed in vivo. Мacrophages isolated from peritoneal
exudate of treated animals showed cytotoxic activity, what was in line with demonstrated
expression of M1 phenotype markers, as well as production of nitric oxide.
Additonally, the phagocytic activity of these cells was preserved. Having in mind lack
of data in the literature concerning the effects of this group of agents on components
of the innate immune system, tubugi 1 remains worthy of further research in the field
of experimental oncology., Тубулизини су природна једињења изолована из родова миксобактерија.
Спадају у групу антимитотских агенаса будући да свој антитуморски ефекат
остварују на нивоу деобног вретена. У овој студији испитиван је антитумор-
ски потенцијал синтетског аналога тубулизина, тубуги 1, in vitro и in vivo на
моделу мишјег меланома. Тубуги 1 је на дозно-зависан начин смањио вијаби-
литет B16 ћелија. Експериментално једињење је у овим ћелијама индуковало
атипичну форму апоптотске ћелијске смрти без екстернализације фосфати-
дилсерина (ПС). Иако је апоптоза била праћена снажном продукцијом ре-
активних врста кисеоника и азота, смањење садржаја малонилдиалдехида је
показало да мембрански липиди нису подлегли оксидацији, што је предуслов
за екстернализацију ПС. Иако ПС има кључну улогу у уклањању апоптотских
ћелија, ово се није одразило на фагоцитну активност макрофага in vitro, ука-
зујући на фагоцитозу независну од ПС. Учинак експерименталног агенса је
потврђен in vivo. Макрофаги изоловани из перитонеалног ексудата третира-
них животиња показали су цитотоксичну активност, што је у сагласности са
показаном експресијом маркера М1 фенотипа и продукцијом азот моноксида.
Додатно, фагоцитна способност ових ћелија је била очувана. С обзиром на
недостатак података у литератури о деловању овакве групе агенаса на компо-
ненте урођеног имунског система, тубуги 1 остаје вредан даљих испитивања
на пољу 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 = "New aspects of synthetic tubulysin derivative, tubugi 1, action in murine melanoma model",
pages = "41-42",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5292"
}

Drača, D., Mijatović, S., Krajnović, T., Bogdanović Pristov, J., Đukić, T., Kaluđerović, G. N., Wessjohann, L. A.,& Maksimović-Ivanić, D.. (2022). New aspects of synthetic tubulysin derivative, tubugi 1, action in murine melanoma model. 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., 41.
https://hdl.handle.net/21.15107/rcub_ibiss_5292

Drača D, Mijatović S, Krajnović T, Bogdanović Pristov J, Đukić T, Kaluđerović GN, Wessjohann LA, Maksimović-Ivanić D. New aspects of synthetic tubulysin derivative, tubugi 1, action in murine melanoma model. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina. 2022;:41.
https://hdl.handle.net/21.15107/rcub_ibiss_5292 .

Drača, Dijana, Mijatović, Sanja, Krajnović, Tamara, Bogdanović Pristov, Jelena, Đukić, Tatjana, Kaluđerović, Goran N., Wessjohann, Ludger A., Maksimović-Ivanić, Danijela, "New aspects of synthetic tubulysin derivative, tubugi 1, action in murine melanoma model" in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina (2022):41,
https://hdl.handle.net/21.15107/rcub_ibiss_5292 .

TY  - CONF
AU  - Krajnović, Tamara
AU  - Drača, Dijana
AU  - Kaluđerović, Goran N.
AU  - Dunđerović, Duško
AU  - Mirkov, Ivana
AU  - Wessjohann, Ludger A.
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5291
AB  - A prenylflavonoid from hops, isoxanthohumol (IXN) is gaining a lot of attention
nowadays due to its broad spectrum of biological activities. This study aimed to investigate
its potential antimetastatic properties in vitro against the highly invasive melanoma
cell line B16-F10 and in a murine metastatic model in vivo, in the context of
independent action and interaction with chemotherapy. The treatment with IXN diminished
cell viability in a dose-dependent manner, which is a consequence of induced
combined cell death by autophagy and caspase-dependent apoptosis. Additionally, the
dividing potential of highly proliferative melanoma cells was dramatically affected by
IXN, and is in line with an abrogated clonogenic potential in the population of survived
cells, indicating changes in their metastatic features. Concordantly, IXN strongly diminished
cell metastatic features down-regulating adhesion, migration, and invasion
through disrupted integrin signaling. Separate application of IXN inhibited the development
of lung metastatic foci in tumor-challenged animals. Although IXN potentiated
the action of chemotherapeutic drug paclitaxel (PCT) in vitro, the concomitant
treatment of these two agents did not exert statistically significant suppression of lung
metastases formation. Nonetheless, the change in the regime of drugs’ application to
7-day treatment with IXN prior to PCT made the subtherapeutic dose of PCT effective,
indicating IXNs’ capacity to trigger the differentiation of B16-F10 cells toward a less
invasive phenotype, thus sensitizing them to chemotherapy. Along with histopathological
confirmation of changes in cell phenotype in metastases, this data underlines the
important impact of the differentiation process on chemotherapy efficacy. This study
represents the first proof of IXNs’ antimetastatic activity in vivo and significantly contributes
to the development of the differentiation therapy concept as a support in the
treatment of metastatic malignancies.
AB  - Пренилфлавоноид из хмеља, изоксантохумол (IXN) данас привлачи велику
пажњу због свог широког спектра биолошких активности. Ова студија је имала
за циљ да истражи његова потенцијална антиметастатска својства на високо ин-
вазивној ћелијској линији меланома B16-F10 in vitro и in vivo, у контексту њего-
вог самосталног деловања или у комбинацији са хемотерапијом. Третман IXN је
смањио вијабилитет ћелија меланома на дозно зависан начин, што је последица
индуковане комбиноване ћелијске смрти аутофагијом и апоптозом зависном од
каспаза. Поред тога, овај изофлаванон је снажно инхибирао деобу високо про-
лиферативних ћелија меланома као и клоногени потенцијал преживелих ћели-
ја, указујући на промене у њиховим метастатским карактеристикама. Сагласно
томе, IXN је супримирао процесе који дефинишу метастазирање као што су
ћелијска адхезија, миграција и инвазија, ометајући интегрински сигнални пут.
Примена IXN је инхибирала развој метастатских жаришта у плућима експери-
менталних животиња. Иако је IXN појачао дејство хемотерапеутика паклитаксе-
ла (PCT) in vitro, истовремени третман ова два агенса није довео до статистички
значајне супресије у формирању плућних метастаза. Са друге стране, промена
динамике давања агенаса у виду 7-дневног третмана животиња IXN пре апли-
кације PCT учинила је ефикасном субтерапеутску дозу PCT, што се може при-
писати његовом капацитету да диферентује B16-F10 ћелије ка мање инвазивном
фенотипу и тиме их сензитизује на хемотерапију. Уз хистопатолошку потврду
промене фенотипа ћелија у метастазама, овај податак указује на значајан до-
принос процеса диференцијације успешности исхода хемотерапије. Ова студија
представља први доказ антиметастатске активности IXN in vivo и значајно до-
приноси успостављању концепта диференцијационе терапије у подршци лечењу
метастатских малигнитета.
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  - Antimetastatic effect of prenylfavonoid isoxanthohumol on b16-f10 murine melanoma model
SP  - 152
EP  - 153
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5291
ER  - 

@conference{
author = "Krajnović, Tamara and Drača, Dijana and Kaluđerović, Goran N. and Dunđerović, Duško and Mirkov, Ivana and Wessjohann, Ludger A. and Maksimović-Ivanić, Danijela and Mijatović, Sanja",
year = "2022",
abstract = "A prenylflavonoid from hops, isoxanthohumol (IXN) is gaining a lot of attention
nowadays due to its broad spectrum of biological activities. This study aimed to investigate
its potential antimetastatic properties in vitro against the highly invasive melanoma
cell line B16-F10 and in a murine metastatic model in vivo, in the context of
independent action and interaction with chemotherapy. The treatment with IXN diminished
cell viability in a dose-dependent manner, which is a consequence of induced
combined cell death by autophagy and caspase-dependent apoptosis. Additionally, the
dividing potential of highly proliferative melanoma cells was dramatically affected by
IXN, and is in line with an abrogated clonogenic potential in the population of survived
cells, indicating changes in their metastatic features. Concordantly, IXN strongly diminished
cell metastatic features down-regulating adhesion, migration, and invasion
through disrupted integrin signaling. Separate application of IXN inhibited the development
of lung metastatic foci in tumor-challenged animals. Although IXN potentiated
the action of chemotherapeutic drug paclitaxel (PCT) in vitro, the concomitant
treatment of these two agents did not exert statistically significant suppression of lung
metastases formation. Nonetheless, the change in the regime of drugs’ application to
7-day treatment with IXN prior to PCT made the subtherapeutic dose of PCT effective,
indicating IXNs’ capacity to trigger the differentiation of B16-F10 cells toward a less
invasive phenotype, thus sensitizing them to chemotherapy. Along with histopathological
confirmation of changes in cell phenotype in metastases, this data underlines the
important impact of the differentiation process on chemotherapy efficacy. This study
represents the first proof of IXNs’ antimetastatic activity in vivo and significantly contributes
to the development of the differentiation therapy concept as a support in the
treatment of metastatic malignancies., Пренилфлавоноид из хмеља, изоксантохумол (IXN) данас привлачи велику
пажњу због свог широког спектра биолошких активности. Ова студија је имала
за циљ да истражи његова потенцијална антиметастатска својства на високо ин-
вазивној ћелијској линији меланома B16-F10 in vitro и in vivo, у контексту њего-
вог самосталног деловања или у комбинацији са хемотерапијом. Третман IXN је
смањио вијабилитет ћелија меланома на дозно зависан начин, што је последица
индуковане комбиноване ћелијске смрти аутофагијом и апоптозом зависном од
каспаза. Поред тога, овај изофлаванон је снажно инхибирао деобу високо про-
лиферативних ћелија меланома као и клоногени потенцијал преживелих ћели-
ја, указујући на промене у њиховим метастатским карактеристикама. Сагласно
томе, IXN је супримирао процесе који дефинишу метастазирање као што су
ћелијска адхезија, миграција и инвазија, ометајући интегрински сигнални пут.
Примена IXN је инхибирала развој метастатских жаришта у плућима експери-
менталних животиња. Иако је IXN појачао дејство хемотерапеутика паклитаксе-
ла (PCT) in vitro, истовремени третман ова два агенса није довео до статистички
значајне супресије у формирању плућних метастаза. Са друге стране, промена
динамике давања агенаса у виду 7-дневног третмана животиња IXN пре апли-
кације PCT учинила је ефикасном субтерапеутску дозу PCT, што се може при-
писати његовом капацитету да диферентује B16-F10 ћелије ка мање инвазивном
фенотипу и тиме их сензитизује на хемотерапију. Уз хистопатолошку потврду
промене фенотипа ћелија у метастазама, овај податак указује на значајан до-
принос процеса диференцијације успешности исхода хемотерапије. Ова студија
представља први доказ антиметастатске активности IXN in vivo и значајно до-
приноси успостављању концепта диференцијационе терапије у подршци лечењу
метастатских малигнитета.",
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 = "Antimetastatic effect of prenylfavonoid isoxanthohumol on b16-f10 murine melanoma model",
pages = "152-153",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5291"
}

Krajnović, T., Drača, D., Kaluđerović, G. N., Dunđerović, D., Mirkov, I., Wessjohann, L. A., Maksimović-Ivanić, D.,& Mijatović, S.. (2022). Antimetastatic effect of prenylfavonoid isoxanthohumol on b16-f10 murine melanoma model. 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., 152-153.
https://hdl.handle.net/21.15107/rcub_ibiss_5291

Krajnović T, Drača D, Kaluđerović GN, Dunđerović D, Mirkov I, Wessjohann LA, Maksimović-Ivanić D, Mijatović S. Antimetastatic effect of prenylfavonoid isoxanthohumol on b16-f10 murine melanoma model. in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina. 2022;:152-153.
https://hdl.handle.net/21.15107/rcub_ibiss_5291 .

Krajnović, Tamara, Drača, Dijana, Kaluđerović, Goran N., Dunđerović, Duško, Mirkov, Ivana, Wessjohann, Ludger A., Maksimović-Ivanić, Danijela, Mijatović, Sanja, "Antimetastatic effect of prenylfavonoid isoxanthohumol on b16-f10 murine melanoma model" in Abstract Book: First Serbian molecular medicine congress; 2022 Jun 16-18; Foča, Bosnia and Herzegovina (2022):152-153,
https://hdl.handle.net/21.15107/rcub_ibiss_5291 .

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  - Drača, Dijana
AU  - Predarska, Ivana
AU  - Komazec, Teodora
AU  - Mihajlović, Ekatarina
AU  - Kaluđerović, Goran N.
AU  - Mijatović, Sanja
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5288
AB  - Severe side effects and drug resistance are the main obstacles in clinical usage of cisplatin. The preparation of platinum(IV) prodrugs and the use of nanoparticles might be potential paths for overcoming the problem of toxicity. Caffeic acid is plant metabolite with many pharmacological effects such as antiinflammatory, anticancer, and hepatoprotective1. In this study, a hybrid molecule build up from cisplatin and acetylated caffeic acid, free and loaded into nanoparticles, SBA-15, was evaluated as an anticancer agent. Cytotoxic studies revealed that free conjugate possessed similar activity as cisplatin alone against 4T1 cell line, while upon imobilisation in SBA-15, much improved cytotoxicity was noticed. Further investigation showed that these compounds induced caspase-dependent apoptosis and an accumulation of cells in the subG compartment of the cell cycle. Intensive production of oxygen and nitrogen radicals was also observed. Also, survived clones lost their dividing potential. Mode of action of this cisplatin-caffeic acid conjugate against 4T1 cells makes it valuable in futher research, from the side of enhancement of its antitumour activity upon mobilisation into nanoparticles and potential reduced toxicity in vivo.
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  - Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate
SP  - 62
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5288
ER  - 

@conference{
author = "Drača, Dijana and Predarska, Ivana and Komazec, Teodora and Mihajlović, Ekatarina and Kaluđerović, Goran N. and Mijatović, Sanja and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "Severe side effects and drug resistance are the main obstacles in clinical usage of cisplatin. The preparation of platinum(IV) prodrugs and the use of nanoparticles might be potential paths for overcoming the problem of toxicity. Caffeic acid is plant metabolite with many pharmacological effects such as antiinflammatory, anticancer, and hepatoprotective1. In this study, a hybrid molecule build up from cisplatin and acetylated caffeic acid, free and loaded into nanoparticles, SBA-15, was evaluated as an anticancer agent. Cytotoxic studies revealed that free conjugate possessed similar activity as cisplatin alone against 4T1 cell line, while upon imobilisation in SBA-15, much improved cytotoxicity was noticed. Further investigation showed that these compounds induced caspase-dependent apoptosis and an accumulation of cells in the subG compartment of the cell cycle. Intensive production of oxygen and nitrogen radicals was also observed. Also, survived clones lost their dividing potential. Mode of action of this cisplatin-caffeic acid conjugate against 4T1 cells makes it valuable in futher research, from the side of enhancement of its antitumour activity upon mobilisation into nanoparticles and potential reduced toxicity in vivo.",
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 = "Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate",
pages = "62",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5288"
}

Drača, D., Predarska, I., Komazec, T., Mihajlović, E., Kaluđerović, G. N., Mijatović, S., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2022). Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate. 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., 62.
https://hdl.handle.net/21.15107/rcub_ibiss_5288

Drača D, Predarska I, Komazec T, Mihajlović E, Kaluđerović GN, Mijatović S, Hey-Hawkins E, Maksimović-Ivanić D. Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:62.
https://hdl.handle.net/21.15107/rcub_ibiss_5288 .

Drača, Dijana, Predarska, Ivana, Komazec, Teodora, Mihajlović, Ekatarina, Kaluđerović, Goran N., Mijatović, Sanja, Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Mesoporous silica nanoparticles improve the antitumour activity of cisplatin-acetylated caffeic acid conjugate" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):62,
https://hdl.handle.net/21.15107/rcub_ibiss_5288 .

TY  - CONF
AU  - Mihajlović, Ekatarina
AU  - Drača, Dijana
AU  - Komazec, Teodora
AU  - Mijatović, Sanja
AU  - Predarska, Ivana
AU  - Kaluđerović, Goran N.
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5287
AB  - To develop anticancer drugs with higher activity and reduced toxicity, cisplatin was used as a scaffold to bear the anti-inflammatory drug naproxen and this conjugate was loaded into silica nanoparticles, SBA-15. In this study, the cytotoxic effect of the free conjugate and the one loaded in SBA-15 was evaluated on different cancer cell lines of mouse origin (B16, 4T1, CT26 and MC38). Treatment with free, as well as with SBA-15-bound conjugate, dose-dependently decreased viability of all cancer cell lines. The viability decrease of B16 cells after treatment with both agents was not caused by apoptosis, but it was followed by caspase activation. On the other hand, treatment with both agents caused significant decrease of B16 cells division rate, indicating the primary cytostatic effect of these agents. Additionally, it was shown that treatment with the free conjugate caused intensified autophagy, while the conjugate loaded into SBA-15 did not show this effect. Since the viability of cells recovered upon the exposure to 3-methyl adenine, detected autophagy serves as a cell death mechanism. Overall, these results indicate that both nacked and immobilized conjugates show great potential for cancer treatment.
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  - Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15
SP  - 99
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5287
ER  - 

@conference{
author = "Mihajlović, Ekatarina and Drača, Dijana and Komazec, Teodora and Mijatović, Sanja and Predarska, Ivana and Kaluđerović, Goran N. and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "To develop anticancer drugs with higher activity and reduced toxicity, cisplatin was used as a scaffold to bear the anti-inflammatory drug naproxen and this conjugate was loaded into silica nanoparticles, SBA-15. In this study, the cytotoxic effect of the free conjugate and the one loaded in SBA-15 was evaluated on different cancer cell lines of mouse origin (B16, 4T1, CT26 and MC38). Treatment with free, as well as with SBA-15-bound conjugate, dose-dependently decreased viability of all cancer cell lines. The viability decrease of B16 cells after treatment with both agents was not caused by apoptosis, but it was followed by caspase activation. On the other hand, treatment with both agents caused significant decrease of B16 cells division rate, indicating the primary cytostatic effect of these agents. Additionally, it was shown that treatment with the free conjugate caused intensified autophagy, while the conjugate loaded into SBA-15 did not show this effect. Since the viability of cells recovered upon the exposure to 3-methyl adenine, detected autophagy serves as a cell death mechanism. Overall, these results indicate that both nacked and immobilized conjugates show great potential for cancer treatment.",
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 = "Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15",
pages = "99",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5287"
}

Mihajlović, E., Drača, D., Komazec, T., Mijatović, S., Predarska, I., Kaluđerović, G. N., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2022). Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15. 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., 99.
https://hdl.handle.net/21.15107/rcub_ibiss_5287

Mihajlović E, Drača D, Komazec T, Mijatović S, Predarska I, Kaluđerović GN, Hey-Hawkins E, Maksimović-Ivanić D. Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:99.
https://hdl.handle.net/21.15107/rcub_ibiss_5287 .

Mihajlović, Ekatarina, Drača, Dijana, Komazec, Teodora, Mijatović, Sanja, Predarska, Ivana, Kaluđerović, Goran N., Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Anticancer properties of cisplatin-naproxen conjugate: free and loaded in SBA-15" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):99,
https://hdl.handle.net/21.15107/rcub_ibiss_5287 .

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  - Komazec, Teodora
AU  - Drača, Dijana
AU  - Mijatović, Sanja
AU  - Predarska, Ivana
AU  - Kaluđerović, Goran N.
AU  - Hey-Hawkins, Evamarie
AU  - Maksimović-Ivanić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5284
AB  - From its discovery, cisplatin therapy has widely been associated with toxicity and severe side effects. Platinum(IV) complexes, as well as immobilising them in nanomaterials could help to overcome these problems. Cyclooxygenase-2 (COX-2) is involved in cancer progresssion,1 which encourages the development of inhibitors of COX enzymes in antitumour therapy. To determine the potential cytotoxic effect, a cisplatin-ibuprofen conjugate in free form, as well as loaded into SBA-15 nanomaterial, was tested on 4T1, CT26, B16 and MC38 cell lines. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and crystal violet viability assays showed that both agents dose-dependently decreased the number of viable cells of all tested cell lines. Flow cytometric analysis revealed significant decrease in the division potential of B16-treated cells. In further investigations, activation of caspases proved by ApoStat assay was noticed; however, apoptosis was not identified by flow cytometry in culture of treated B16 cells. Finally, light microscopy evaluation revealed the presence of enlarged cells with prominent heterochromatin foci in nuclei upon the treatment indicating that cells entered senescent state. High antitumour potential defined at the nanomolar concentration on mouse melanoma cells make cisplatin-ibuprofen a suitable candidate for further research.
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  - Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines
SP  - 83
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5284
ER  - 

@conference{
author = "Komazec, Teodora and Drača, Dijana and Mijatović, Sanja and Predarska, Ivana and Kaluđerović, Goran N. and Hey-Hawkins, Evamarie and Maksimović-Ivanić, Danijela",
year = "2022",
abstract = "From its discovery, cisplatin therapy has widely been associated with toxicity and severe side effects. Platinum(IV) complexes, as well as immobilising them in nanomaterials could help to overcome these problems. Cyclooxygenase-2 (COX-2) is involved in cancer progresssion,1 which encourages the development of inhibitors of COX enzymes in antitumour therapy. To determine the potential cytotoxic effect, a cisplatin-ibuprofen conjugate in free form, as well as loaded into SBA-15 nanomaterial, was tested on 4T1, CT26, B16 and MC38 cell lines. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and crystal violet viability assays showed that both agents dose-dependently decreased the number of viable cells of all tested cell lines. Flow cytometric analysis revealed significant decrease in the division potential of B16-treated cells. In further investigations, activation of caspases proved by ApoStat assay was noticed; however, apoptosis was not identified by flow cytometry in culture of treated B16 cells. Finally, light microscopy evaluation revealed the presence of enlarged cells with prominent heterochromatin foci in nuclei upon the treatment indicating that cells entered senescent state. High antitumour potential defined at the nanomolar concentration on mouse melanoma cells make cisplatin-ibuprofen a suitable candidate for further research.",
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 = "Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines",
pages = "83",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5284"
}

Komazec, T., Drača, D., Mijatović, S., Predarska, I., Kaluđerović, G. N., Hey-Hawkins, E.,& Maksimović-Ivanić, D.. (2022). Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines. 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., 83.
https://hdl.handle.net/21.15107/rcub_ibiss_5284

Komazec T, Drača D, Mijatović S, Predarska I, Kaluđerović GN, Hey-Hawkins E, Maksimović-Ivanić D. Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines. in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia. 2022;:83.
https://hdl.handle.net/21.15107/rcub_ibiss_5284 .

Komazec, Teodora, Drača, Dijana, Mijatović, Sanja, Predarska, Ivana, Kaluđerović, Goran N., Hey-Hawkins, Evamarie, Maksimović-Ivanić, Danijela, "Cisplatin-ibuprofen conjugate free and immobilised in mesoporous silica nanoparticle SBA-15 indicate high antiproliferative potential on mouse cancer cell lines" in Proceedings: Serbian Biochemical Society, Eleventh Conference, Scientific meeting of an international character: "Amazing Biochemistry"; 2022 Sep 22-23; Novi Sad, Serbia (2022):83,
https://hdl.handle.net/21.15107/rcub_ibiss_5284 .

TY  - JOUR
AU  - Drača, Dijana
AU  - Edeler, David
AU  - Saoud, Mohamad
AU  - Dojčinović, Biljana
AU  - Dunđerović, Duško
AU  - Đmura, Goran
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Kaluđerović, Goran N.
PY  - 2021
UR  - internal-pdf://Drača et al. - 2021 - Antitumor potential of cisplatin loaded into SBA-15 mesoporous silica nanoparticles against B16F1 melanoma cells i.pdf
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0162013421000301
UR  - http://www.ncbi.nlm.nih.gov/pubmed/33582397
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4154
AB  - CP (cisplatin) and mesoporous silica SBA-15 (Santa Barbara amorphous 15) loaded with CP (→SBA-15|CP) were tested in vitro and in vivo against low metastatic mouse melanoma B16F1 cell line. SBA-15 only, as drug carrier, is found to be not active, while CP and SBA-15|CP revealed high cytotoxicity in lower μM range. The activity of SBA-15|CP was found similar to the activity of CP alone. Both CP and SBA-15|CP induced inhibition of cell proliferation (carboxyfluorescein succinimidyl ester - CFSE assay) along with G2/M arrest (4',6-diamidino-2-phenylindole - DAPI assay). Apoptosis (Annexin V/ propidium iodide - PI assay), through caspase activation (apostat assay) and nitric oxide (NO) production (diacetate(4-amino-5-methylamino-2',7'-difluorofluorescein-diacetat) - DAF FM assay), was identified as main mode of cell death. However, slight elevated autophagy (acridine orange - AO assay) was detected in treated B16F1 cells. CP and SBA-15|CP did not affect production of ROS (reactive oxygen species) in B16F1 cells. Both SBA-15|CP and CP induced in B16F1 G2 arrest and subsequent senescence. SBA-15|CP, but not CP, blocked the growth of melanoma in C57BL/6 mice. Moreover, hepato- and nephrotoxicity in SBA-15|CP treated animals were diminished in comparison to CP confirming multiply improved antitumor potential of immobilized CP. Outstandingly, SBA-15 boosted in vivo activity and diminished side effects of CP.
PB  - Elsevier BV
T2  - Journal of Inorganic Biochemistry
T1  - Antitumor potential of cisplatin loaded into SBA-15 mesoporous silica nanoparticles against B16F1 melanoma cells: in vitro and in vivo studies.
VL  - 217
DO  - 10.1016/j.jinorgbio.2021.111383
SP  - 111383
ER  - 

@article{
author = "Drača, Dijana and Edeler, David and Saoud, Mohamad and Dojčinović, Biljana and Dunđerović, Duško and Đmura, Goran and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Kaluđerović, Goran N.",
year = "2021",
abstract = "CP (cisplatin) and mesoporous silica SBA-15 (Santa Barbara amorphous 15) loaded with CP (→SBA-15|CP) were tested in vitro and in vivo against low metastatic mouse melanoma B16F1 cell line. SBA-15 only, as drug carrier, is found to be not active, while CP and SBA-15|CP revealed high cytotoxicity in lower μM range. The activity of SBA-15|CP was found similar to the activity of CP alone. Both CP and SBA-15|CP induced inhibition of cell proliferation (carboxyfluorescein succinimidyl ester - CFSE assay) along with G2/M arrest (4',6-diamidino-2-phenylindole - DAPI assay). Apoptosis (Annexin V/ propidium iodide - PI assay), through caspase activation (apostat assay) and nitric oxide (NO) production (diacetate(4-amino-5-methylamino-2',7'-difluorofluorescein-diacetat) - DAF FM assay), was identified as main mode of cell death. However, slight elevated autophagy (acridine orange - AO assay) was detected in treated B16F1 cells. CP and SBA-15|CP did not affect production of ROS (reactive oxygen species) in B16F1 cells. Both SBA-15|CP and CP induced in B16F1 G2 arrest and subsequent senescence. SBA-15|CP, but not CP, blocked the growth of melanoma in C57BL/6 mice. Moreover, hepato- and nephrotoxicity in SBA-15|CP treated animals were diminished in comparison to CP confirming multiply improved antitumor potential of immobilized CP. Outstandingly, SBA-15 boosted in vivo activity and diminished side effects of CP.",
publisher = "Elsevier BV",
journal = "Journal of Inorganic Biochemistry",
title = "Antitumor potential of cisplatin loaded into SBA-15 mesoporous silica nanoparticles against B16F1 melanoma cells: in vitro and in vivo studies.",
volume = "217",
doi = "10.1016/j.jinorgbio.2021.111383",
pages = "111383"
}

Drača, D., Edeler, D., Saoud, M., Dojčinović, B., Dunđerović, D., Đmura, G., Maksimović-Ivanić, D., Mijatović, S.,& Kaluđerović, G. N.. (2021). Antitumor potential of cisplatin loaded into SBA-15 mesoporous silica nanoparticles against B16F1 melanoma cells: in vitro and in vivo studies.. in Journal of Inorganic Biochemistry
Elsevier BV., 217, 111383.
https://doi.org/10.1016/j.jinorgbio.2021.111383

Drača D, Edeler D, Saoud M, Dojčinović B, Dunđerović D, Đmura G, Maksimović-Ivanić D, Mijatović S, Kaluđerović GN. Antitumor potential of cisplatin loaded into SBA-15 mesoporous silica nanoparticles against B16F1 melanoma cells: in vitro and in vivo studies.. in Journal of Inorganic Biochemistry. 2021;217:111383.
doi:10.1016/j.jinorgbio.2021.111383 .

Drača, Dijana, Edeler, David, Saoud, Mohamad, Dojčinović, Biljana, Dunđerović, Duško, Đmura, Goran, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Kaluđerović, Goran N., "Antitumor potential of cisplatin loaded into SBA-15 mesoporous silica nanoparticles against B16F1 melanoma cells: in vitro and in vivo studies." in Journal of Inorganic Biochemistry, 217 (2021):111383,
https://doi.org/10.1016/j.jinorgbio.2021.111383 . .

TY  - JOUR
AU  - Saretz, Stefan
AU  - Basset, Gabriele
AU  - Useini, Liridona
AU  - Laube, Markus
AU  - Pietzsch, Jens
AU  - Drača, Dijana
AU  - Maksimović-Ivanić, Danijela
AU  - Trambauer, Johannes
AU  - Steiner, Harald
AU  - Hey-Hawkins, Evamarie
PY  - 2021
UR  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151329/
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4250
AB  - All over the world, societies are facing rapidly aging populations combined with a growing number of patients suffering from Alzheimer’s disease (AD). One focus in pharmaceutical research to address this issue is on the reduction of the longer amyloid-β (Aβ) fragments in the brain by modulation of γ-secretase, a membrane-bound protease. R-Flurbiprofen (tarenflurbil) was studied in this regard but failed to show significant improvement in AD patients in a phase 3 clinical trial. This was mainly attributed to its low ability to cross the blood–brain barrier (BBB). Here, we present the synthesis and in vitro evaluation of a racemic meta-carborane analogue of flurbiprofen. By introducing the carborane moiety, the hydrophobicity could be shifted into a more favourable range for the penetration of the blood–brain barrier, evident by a logD7.4 value of 2.0. Furthermore, our analogue retained γ-secretase modulator activity in comparison to racemic flurbiprofen in a cell-based assay. These findings demonstrate the potential of carboranes as phenyl mimetics also in AD research.
PB  - MDPI AG
T2  - Molecules
T1  - Modulation of γ-Secretase Activity by a Carborane-Based Flurbiprofen Analogue
IS  - 10
VL  - 26
DO  - 10.3390/molecules26102843
SP  - 2843
ER  - 

@article{
author = "Saretz, Stefan and Basset, Gabriele and Useini, Liridona and Laube, Markus and Pietzsch, Jens and Drača, Dijana and Maksimović-Ivanić, Danijela and Trambauer, Johannes and Steiner, Harald and Hey-Hawkins, Evamarie",
year = "2021",
abstract = "All over the world, societies are facing rapidly aging populations combined with a growing number of patients suffering from Alzheimer’s disease (AD). One focus in pharmaceutical research to address this issue is on the reduction of the longer amyloid-β (Aβ) fragments in the brain by modulation of γ-secretase, a membrane-bound protease. R-Flurbiprofen (tarenflurbil) was studied in this regard but failed to show significant improvement in AD patients in a phase 3 clinical trial. This was mainly attributed to its low ability to cross the blood–brain barrier (BBB). Here, we present the synthesis and in vitro evaluation of a racemic meta-carborane analogue of flurbiprofen. By introducing the carborane moiety, the hydrophobicity could be shifted into a more favourable range for the penetration of the blood–brain barrier, evident by a logD7.4 value of 2.0. Furthermore, our analogue retained γ-secretase modulator activity in comparison to racemic flurbiprofen in a cell-based assay. These findings demonstrate the potential of carboranes as phenyl mimetics also in AD research.",
publisher = "MDPI AG",
journal = "Molecules",
title = "Modulation of γ-Secretase Activity by a Carborane-Based Flurbiprofen Analogue",
number = "10",
volume = "26",
doi = "10.3390/molecules26102843",
pages = "2843"
}

Saretz, S., Basset, G., Useini, L., Laube, M., Pietzsch, J., Drača, D., Maksimović-Ivanić, D., Trambauer, J., Steiner, H.,& Hey-Hawkins, E.. (2021). Modulation of γ-Secretase Activity by a Carborane-Based Flurbiprofen Analogue. in Molecules
MDPI AG., 26(10), 2843.
https://doi.org/10.3390/molecules26102843

Saretz S, Basset G, Useini L, Laube M, Pietzsch J, Drača D, Maksimović-Ivanić D, Trambauer J, Steiner H, Hey-Hawkins E. Modulation of γ-Secretase Activity by a Carborane-Based Flurbiprofen Analogue. in Molecules. 2021;26(10):2843.
doi:10.3390/molecules26102843 .

Saretz, Stefan, Basset, Gabriele, Useini, Liridona, Laube, Markus, Pietzsch, Jens, Drača, Dijana, Maksimović-Ivanić, Danijela, Trambauer, Johannes, Steiner, Harald, Hey-Hawkins, Evamarie, "Modulation of γ-Secretase Activity by a Carborane-Based Flurbiprofen Analogue" in Molecules, 26, no. 10 (2021):2843,
https://doi.org/10.3390/molecules26102843 . .

TY  - JOUR
AU  - De Palo, Alice
AU  - Drača, Dijana
AU  - Murrali, Maria Grazia
AU  - Zacchini, Stefano
AU  - Pampaloni, Guido
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Marchetti, Fabio
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4424
AB  - Piano-stool iridium complexes based on the pentamethylcyclopentadienyl ligand (Cp*)
have been intensively investigated as anticancer drug candidates and hold much promise in this
setting. A systematic study aimed at outlining the effect of Cp* mono-derivatization on the an tiproliferative activity is presented here. Thus, the dinuclear complexes [Ir(η
5
-C5Me4R)Cl(µ-Cl)]2
(R = Me, 1a; R = H, 1b; R = Pr, 1c; R = 4-C6H4F, 1d; R = 4-C6H4OH, 1e), their 2-phenylpyridyl
mononuclear derivatives [Ir(η
5
-C5Me4R)(kN,kCPhPy)Cl] (2a–d), and the dimethylsulfoxide complex
[Ir{η
5
-C5Me4
(4-C6H4OH)}Cl2
(κS-Me2S=O)] (3) were synthesized, structurally characterized, and
assessed for their cytotoxicity towards a panel of six human and rodent cancer cell lines (mouse
melanoma, B16; rat glioma, C6; breast adenocarcinoma, MCF-7; colorectal carcinoma, SW620 and
HCT116; ovarian carcinoma, A2780) and one primary, human fetal lung fibroblast cell line (MRC5).
Complexes 2b (R = H) and 2d (4-C6H4F) emerged as the most active ones and were selected for further
investigation. They did not affect the viability of primary mouse peritoneal cells, and their tumorici dal action arises from the combined influence on cellular proliferation, apoptosis and senescence. The
latter is triggered by mitochondrial failure and production of reactive oxygen and nitrogen species.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η 5 -C5Me4R} Complexes with Variable R Groups
IS  - 14
VL  - 22
DO  - 10.3390/ijms22147422
SP  - 7422
ER  - 

@article{
author = "De Palo, Alice and Drača, Dijana and Murrali, Maria Grazia and Zacchini, Stefano and Pampaloni, Guido and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Marchetti, Fabio",
year = "2021",
abstract = "Piano-stool iridium complexes based on the pentamethylcyclopentadienyl ligand (Cp*)
have been intensively investigated as anticancer drug candidates and hold much promise in this
setting. A systematic study aimed at outlining the effect of Cp* mono-derivatization on the an tiproliferative activity is presented here. Thus, the dinuclear complexes [Ir(η
5
-C5Me4R)Cl(µ-Cl)]2
(R = Me, 1a; R = H, 1b; R = Pr, 1c; R = 4-C6H4F, 1d; R = 4-C6H4OH, 1e), their 2-phenylpyridyl
mononuclear derivatives [Ir(η
5
-C5Me4R)(kN,kCPhPy)Cl] (2a–d), and the dimethylsulfoxide complex
[Ir{η
5
-C5Me4
(4-C6H4OH)}Cl2
(κS-Me2S=O)] (3) were synthesized, structurally characterized, and
assessed for their cytotoxicity towards a panel of six human and rodent cancer cell lines (mouse
melanoma, B16; rat glioma, C6; breast adenocarcinoma, MCF-7; colorectal carcinoma, SW620 and
HCT116; ovarian carcinoma, A2780) and one primary, human fetal lung fibroblast cell line (MRC5).
Complexes 2b (R = H) and 2d (4-C6H4F) emerged as the most active ones and were selected for further
investigation. They did not affect the viability of primary mouse peritoneal cells, and their tumorici dal action arises from the combined influence on cellular proliferation, apoptosis and senescence. The
latter is triggered by mitochondrial failure and production of reactive oxygen and nitrogen species.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η 5 -C5Me4R} Complexes with Variable R Groups",
number = "14",
volume = "22",
doi = "10.3390/ijms22147422",
pages = "7422"
}

De Palo, A., Drača, D., Murrali, M. G., Zacchini, S., Pampaloni, G., Mijatović, S., Maksimović-Ivanić, D.,& Marchetti, F.. (2021). A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η 5 -C5Me4R} Complexes with Variable R Groups. in International Journal of Molecular Sciences
Basel: MDPI., 22(14), 7422.
https://doi.org/10.3390/ijms22147422

De Palo A, Drača D, Murrali MG, Zacchini S, Pampaloni G, Mijatović S, Maksimović-Ivanić D, Marchetti F. A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η 5 -C5Me4R} Complexes with Variable R Groups. in International Journal of Molecular Sciences. 2021;22(14):7422.
doi:10.3390/ijms22147422 .

De Palo, Alice, Drača, Dijana, Murrali, Maria Grazia, Zacchini, Stefano, Pampaloni, Guido, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Marchetti, Fabio, "A Comparative Analysis of the In Vitro Anticancer Activity of Iridium(III) {η 5 -C5Me4R} Complexes with Variable R Groups" in International Journal of Molecular Sciences, 22, no. 14 (2021):7422,
https://doi.org/10.3390/ijms22147422 . .

TY  - JOUR
AU  - Drača, Dijana
AU  - Marković, Milan
AU  - Gozzi, Marta
AU  - Mijatović, Sanja
AU  - Maksimović-Ivanić, Danijela
AU  - Hey-Hawkins, Evamarie
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4425
AB  - Gliomas and glioblastomas are very aggressive forms of brain tumors, prone to the devel opment of a multitude of resistance mechanisms to therapeutic treatments, including cytoprotective
autophagy. In this work, we investigated the role and mechanism of action of the combination of a
ruthenacarborane derivative with 8-hydroxyquinoline (8-HQ), linked via an ester bond (complex 2),
in rat astrocytoma C6 and human glioma U251 cells, in comparison with the two compounds alone,
i.e., the free carboxylic acid (complex 1) and 8-HQ, and their non-covalent combination ([1 + 8-HQ],
in 1:1 molar ratio). We found that only complex 2 was able to significantly affect cellular viability
in glioma U251 cells (IC50 11.4 µM) via inhibition of the autophagic machinery, most likely acting
at the early stages of the autophagic cascade. Contrary to 8-HQ alone, complex 2 was also able
to impair cellular viability under conditions of glucose deprivation. We thus suggest different
mechanisms of action of ruthenacarborane complex 2 than purely organic quinoline-based drugs,
making complex 2 a very attractive candidate for evading the known resistances of brain tumors to
chloroquine-based therapies.
PB  - Basel: MDPI
T2  - Molecules
T1  - Ruthenacarborane and Quinoline: A Promising Combination for the Treatment of Brain Tumors
IS  - 13
VL  - 26
DO  - 10.3390/molecules26133801
SP  - 3801
ER  - 

@article{
author = "Drača, Dijana and Marković, Milan and Gozzi, Marta and Mijatović, Sanja and Maksimović-Ivanić, Danijela and Hey-Hawkins, Evamarie",
year = "2021",
abstract = "Gliomas and glioblastomas are very aggressive forms of brain tumors, prone to the devel opment of a multitude of resistance mechanisms to therapeutic treatments, including cytoprotective
autophagy. In this work, we investigated the role and mechanism of action of the combination of a
ruthenacarborane derivative with 8-hydroxyquinoline (8-HQ), linked via an ester bond (complex 2),
in rat astrocytoma C6 and human glioma U251 cells, in comparison with the two compounds alone,
i.e., the free carboxylic acid (complex 1) and 8-HQ, and their non-covalent combination ([1 + 8-HQ],
in 1:1 molar ratio). We found that only complex 2 was able to significantly affect cellular viability
in glioma U251 cells (IC50 11.4 µM) via inhibition of the autophagic machinery, most likely acting
at the early stages of the autophagic cascade. Contrary to 8-HQ alone, complex 2 was also able
to impair cellular viability under conditions of glucose deprivation. We thus suggest different
mechanisms of action of ruthenacarborane complex 2 than purely organic quinoline-based drugs,
making complex 2 a very attractive candidate for evading the known resistances of brain tumors to
chloroquine-based therapies.",
publisher = "Basel: MDPI",
journal = "Molecules",
title = "Ruthenacarborane and Quinoline: A Promising Combination for the Treatment of Brain Tumors",
number = "13",
volume = "26",
doi = "10.3390/molecules26133801",
pages = "3801"
}

Drača, D., Marković, M., Gozzi, M., Mijatović, S., Maksimović-Ivanić, D.,& Hey-Hawkins, E.. (2021). Ruthenacarborane and Quinoline: A Promising Combination for the Treatment of Brain Tumors. in Molecules
Basel: MDPI., 26(13), 3801.
https://doi.org/10.3390/molecules26133801

Drača D, Marković M, Gozzi M, Mijatović S, Maksimović-Ivanić D, Hey-Hawkins E. Ruthenacarborane and Quinoline: A Promising Combination for the Treatment of Brain Tumors. in Molecules. 2021;26(13):3801.
doi:10.3390/molecules26133801 .

Drača, Dijana, Marković, Milan, Gozzi, Marta, Mijatović, Sanja, Maksimović-Ivanić, Danijela, Hey-Hawkins, Evamarie, "Ruthenacarborane and Quinoline: A Promising Combination for the Treatment of Brain Tumors" in Molecules, 26, no. 13 (2021):3801,
https://doi.org/10.3390/molecules26133801 . .

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 . .