TY  - JOUR
AU  - Ludwig, Gerd
AU  - Ranđelović, Ivan
AU  - Dimić, Dušan
AU  - Komazec, Teodora
AU  - Maksimović-Ivanić, Danijela
AU  - Mijatović, Sanja
AU  - Rüffer, Tobias
AU  - Kaluđerović, Goran N.
PY  - 2024
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6642
AB  - The (pentamethylcyclopentadienyl)chloridoiridium(III) complex bearing a κP,κS-bonded Ph2PCH2CH2SPh ligand ([Ir(η5-C5Me5)Cl(Ph2P(CH2)2SPh-κP,κS)]PF6, (1)] was synthesized and characterized. Multinuclear (1H, 13C and 31P) NMR spectroscopy was employed for the determination of the structure. Moreover, SC-XRD confirmed the proposed structure belongs to the “piano stool” type. The Hirshfeld surface analysis outlined the most important intermolecular interactions in the structure. The crystallographic structure was optimized at the B3LYP-D3BJ/6-311++G(d,p)(H,C,P,S,Cl)/LanL2DZ(Ir) level of theory. The applicability of this level was verified through a comparison of experimental and theoretical bond lengths and angles, and 1H and 13C NMR chemical shifts. The Natural Bond Orbital theory was used to identify and quantify the intramolecular stabilization interactions, especially those between donor atoms and Ir(III) ions. Complex 1 was tested on antitumor activity against five human tumor cell lines: MCF-7 breast adenocarcinoma, SW480 colon adenocarcinoma, 518A2 melanoma, 8505C human thyroid carcinoma and A253 submandibular carcinoma. Complex 1 showed superior antitumor activity against cisplatin-resistant MCF-7, SW480 and 8505C cell lines. The mechanism of tumoricidal action on 8505C cells indicates the involvement of caspase-induced apoptosis, accompanied by a considerable reduction in ROS/RNS and proliferation potential of treated cells.
PB  - Basel: MDPI
T2  - Biomolecules
T1  - (Pentamethylcyclopentadienyl)chloridoiridium(III) Complex Bearing Bidentate Ph2PCH2CH2SPh-κP,κS Ligand
IS  - 4
VL  - 14
DO  - 10.3390/biom14040420
SP  - 420
ER  - 

@article{
author = "Ludwig, Gerd and Ranđelović, Ivan and Dimić, Dušan and Komazec, Teodora and Maksimović-Ivanić, Danijela and Mijatović, Sanja and Rüffer, Tobias and Kaluđerović, Goran N.",
year = "2024",
abstract = "The (pentamethylcyclopentadienyl)chloridoiridium(III) complex bearing a κP,κS-bonded Ph2PCH2CH2SPh ligand ([Ir(η5-C5Me5)Cl(Ph2P(CH2)2SPh-κP,κS)]PF6, (1)] was synthesized and characterized. Multinuclear (1H, 13C and 31P) NMR spectroscopy was employed for the determination of the structure. Moreover, SC-XRD confirmed the proposed structure belongs to the “piano stool” type. The Hirshfeld surface analysis outlined the most important intermolecular interactions in the structure. The crystallographic structure was optimized at the B3LYP-D3BJ/6-311++G(d,p)(H,C,P,S,Cl)/LanL2DZ(Ir) level of theory. The applicability of this level was verified through a comparison of experimental and theoretical bond lengths and angles, and 1H and 13C NMR chemical shifts. The Natural Bond Orbital theory was used to identify and quantify the intramolecular stabilization interactions, especially those between donor atoms and Ir(III) ions. Complex 1 was tested on antitumor activity against five human tumor cell lines: MCF-7 breast adenocarcinoma, SW480 colon adenocarcinoma, 518A2 melanoma, 8505C human thyroid carcinoma and A253 submandibular carcinoma. Complex 1 showed superior antitumor activity against cisplatin-resistant MCF-7, SW480 and 8505C cell lines. The mechanism of tumoricidal action on 8505C cells indicates the involvement of caspase-induced apoptosis, accompanied by a considerable reduction in ROS/RNS and proliferation potential of treated cells.",
publisher = "Basel: MDPI",
journal = "Biomolecules",
title = "(Pentamethylcyclopentadienyl)chloridoiridium(III) Complex Bearing Bidentate Ph2PCH2CH2SPh-κP,κS Ligand",
number = "4",
volume = "14",
doi = "10.3390/biom14040420",
pages = "420"
}

Ludwig, G., Ranđelović, I., Dimić, D., Komazec, T., Maksimović-Ivanić, D., Mijatović, S., Rüffer, T.,& Kaluđerović, G. N.. (2024). (Pentamethylcyclopentadienyl)chloridoiridium(III) Complex Bearing Bidentate Ph2PCH2CH2SPh-κP,κS Ligand. in Biomolecules
Basel: MDPI., 14(4), 420.
https://doi.org/10.3390/biom14040420

Ludwig G, Ranđelović I, Dimić D, Komazec T, Maksimović-Ivanić D, Mijatović S, Rüffer T, Kaluđerović GN. (Pentamethylcyclopentadienyl)chloridoiridium(III) Complex Bearing Bidentate Ph2PCH2CH2SPh-κP,κS Ligand. in Biomolecules. 2024;14(4):420.
doi:10.3390/biom14040420 .

Ludwig, Gerd, Ranđelović, Ivan, Dimić, Dušan, Komazec, Teodora, Maksimović-Ivanić, Danijela, Mijatović, Sanja, Rüffer, Tobias, Kaluđerović, Goran N., "(Pentamethylcyclopentadienyl)chloridoiridium(III) Complex Bearing Bidentate Ph2PCH2CH2SPh-κP,κS Ligand" in Biomolecules, 14, no. 4 (2024):420,
https://doi.org/10.3390/biom14040420 . .

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TY  - CONF
AU  - 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  - 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 .