TY  - JOUR
AU  - Đorđević, Dragana B.
AU  - Milovanović, Jelena
AU  - Jurisević, Milena
AU  - Stojanović, Bojana
AU  - Cvetković, Olga
AU  - Pergal, Marija
AU  - Ristanović, Elizabeta
AU  - Vojvodić, Danilo
AU  - Simić, Miloš
AU  - Manojlović, Dragan
AU  - Milovanović, Marija
AU  - Arsenijević, Nebojsa
PY  - 2019
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/3421
AB  - Copper serves as a limiting factor for multiple steps of tumour progression, including angiogenesis, growth and metastasis. High levels of copper have been found in a wide spectrum of human cancers. Antitumour activities of copper-chelating drugs have been reported in animal models. Organosulfur compounds (diallyl sulfide, DAS; diallyl disulfide, DADS; S-ethylcysteine, SEC; N-acetylcysteine, NAC) derived from garlic exhibit marked copper-chelating activity. We analysed a mixture of fifteen n-propyl polysulfides (DPPS) for potential antitumour activity against several murine tumour cell lines, including colon carcinoma (CT26), mammary carcinoma (4T1) and melanoma cell lines (B16F10), and compared the effects with the antiproliferative effect in highly proliferative murine mesenchymal stem cells (mMSCs). The effects of the mixture of n-propyl polysulfides (100%) on cell viability were determined using MTT assays. Cell apoptosis was analysed using Annexin V-FITC/PI assays.The results of the MTT assays indicate that this standardized mixture of n-propyl polysulfides has a strong, dose-dependent cytotoxic effect against all three of the tested tumour cell lines (CT26, 4T1, B16F10). The cytotoxic effect of the n-propyl polysulfide mixture against the CT26 and B16F10 cell lines was much stronger than that of cisplatin and was significantly weaker in mMSCs, which are non-cancerous and highly proliferative cells, than in cancer cells. Flow cytometric analysis of CT26 and 4T1 cells revealed that apoptosis was not the dominant mechanism of cell death induced by the n-propyl polysulfide mixture. The n-propyl polysulfide mixture exerted highly cytotoxic activity against murine colon carcinoma and melanoma cell lines, but its antiproliferative activity against mMSCs was significantly lower than that of cisplatin.
AB  - Bakar učestvuje u različitim fazama progresije tumora, u angiogenezi, rastu i metastaziranju. Povećane vrednosti bakra u serumu i u tkivu tumora, karakteristika su različitih vrsta tumora kod ljudi. U animalnim eksperimentalnim modelima, supstance (lekovi) koje heliraju bakar ispoljavaju anti-tumorski efekat. Helatori bakra su i organosumporna jedinjenja, izolovana iz belog luka. U ovoj studiji analizirali smo potencijalnu anti-tumorsku aktivnost smeše petnaest različitih n-propil polisulfi da na nekoliko mišjih ćelijskih linija tumora: karcinom kolona (CT26), karcinom dojke (4T1) i melanom (B16F10). Aktivnost ove smeše na tumorskim linijama, uporedili smo sa antiproliferativnim efektom na mezenhimalne matične ćelije miša (engl. murine mesenchymal stem cells, mMSC). Efekat smeše n-propil polisulfi da (100%) na vijabilnost ćelija ispitali smo MTT testom. Apoptozu ćelija smo analizirali koristeći Annexin V-FITC/PI test. Rezultati MTT testa ukazuju da standardizovana smeša n-propil polisulfi da ima jak citotoksični, dozno-zavisni, efekat na sve tri testirane ćelijske linije tumora (CT26, 4T1, B16F10). Smeša n-propil polisulfi da ispoljava izraženiji citotoksični efekat na CT26 i B16F10 linije u odnosu na cisplatinu. Citotoksični efekat ove smeše na mMSC je značajno slabiji poredeći sa efektom cisplatine, što ukazuje na selektivnije dejstvo. Analiza CT26 i 4T1 ćelija protočnom citometrijom pokazala je da apoptoza nije glavni oblik smrti ćelija, koju uzrokuje smeša n-propil polisulfi - da. Smeša n-propil polisulfi da ispoljava jaču citotoksičnu aktivnost na ćelijskim linijama mišjeg karcinoma kolona i melanoma i slabiju aktivnost na mMSC u poređenju sa efektom cisplatine.
T2  - Serbian Journal of Experimental and Clinical Research
T1  - Antitumour effect of a mixture of n-propyl polysulfides In vitro
T1  - Antitumorski efekti smeše n-propil polisulfida in vitro
VL  - 20
IS  - 4
SP  - 295
EP  - 300
DO  - 10.1515/sjecr-2017-0069
ER  - 

@article{
author = "Đorđević, Dragana B. and Milovanović, Jelena and Jurisević, Milena and Stojanović, Bojana and Cvetković, Olga and Pergal, Marija and Ristanović, Elizabeta and Vojvodić, Danilo and Simić, Miloš and Manojlović, Dragan and Milovanović, Marija and Arsenijević, Nebojsa",
year = "2019",
abstract = "Copper serves as a limiting factor for multiple steps of tumour progression, including angiogenesis, growth and metastasis. High levels of copper have been found in a wide spectrum of human cancers. Antitumour activities of copper-chelating drugs have been reported in animal models. Organosulfur compounds (diallyl sulfide, DAS; diallyl disulfide, DADS; S-ethylcysteine, SEC; N-acetylcysteine, NAC) derived from garlic exhibit marked copper-chelating activity. We analysed a mixture of fifteen n-propyl polysulfides (DPPS) for potential antitumour activity against several murine tumour cell lines, including colon carcinoma (CT26), mammary carcinoma (4T1) and melanoma cell lines (B16F10), and compared the effects with the antiproliferative effect in highly proliferative murine mesenchymal stem cells (mMSCs). The effects of the mixture of n-propyl polysulfides (100%) on cell viability were determined using MTT assays. Cell apoptosis was analysed using Annexin V-FITC/PI assays.The results of the MTT assays indicate that this standardized mixture of n-propyl polysulfides has a strong, dose-dependent cytotoxic effect against all three of the tested tumour cell lines (CT26, 4T1, B16F10). The cytotoxic effect of the n-propyl polysulfide mixture against the CT26 and B16F10 cell lines was much stronger than that of cisplatin and was significantly weaker in mMSCs, which are non-cancerous and highly proliferative cells, than in cancer cells. Flow cytometric analysis of CT26 and 4T1 cells revealed that apoptosis was not the dominant mechanism of cell death induced by the n-propyl polysulfide mixture. The n-propyl polysulfide mixture exerted highly cytotoxic activity against murine colon carcinoma and melanoma cell lines, but its antiproliferative activity against mMSCs was significantly lower than that of cisplatin., Bakar učestvuje u različitim fazama progresije tumora, u angiogenezi, rastu i metastaziranju. Povećane vrednosti bakra u serumu i u tkivu tumora, karakteristika su različitih vrsta tumora kod ljudi. U animalnim eksperimentalnim modelima, supstance (lekovi) koje heliraju bakar ispoljavaju anti-tumorski efekat. Helatori bakra su i organosumporna jedinjenja, izolovana iz belog luka. U ovoj studiji analizirali smo potencijalnu anti-tumorsku aktivnost smeše petnaest različitih n-propil polisulfi da na nekoliko mišjih ćelijskih linija tumora: karcinom kolona (CT26), karcinom dojke (4T1) i melanom (B16F10). Aktivnost ove smeše na tumorskim linijama, uporedili smo sa antiproliferativnim efektom na mezenhimalne matične ćelije miša (engl. murine mesenchymal stem cells, mMSC). Efekat smeše n-propil polisulfi da (100%) na vijabilnost ćelija ispitali smo MTT testom. Apoptozu ćelija smo analizirali koristeći Annexin V-FITC/PI test. Rezultati MTT testa ukazuju da standardizovana smeša n-propil polisulfi da ima jak citotoksični, dozno-zavisni, efekat na sve tri testirane ćelijske linije tumora (CT26, 4T1, B16F10). Smeša n-propil polisulfi da ispoljava izraženiji citotoksični efekat na CT26 i B16F10 linije u odnosu na cisplatinu. Citotoksični efekat ove smeše na mMSC je značajno slabiji poredeći sa efektom cisplatine, što ukazuje na selektivnije dejstvo. Analiza CT26 i 4T1 ćelija protočnom citometrijom pokazala je da apoptoza nije glavni oblik smrti ćelija, koju uzrokuje smeša n-propil polisulfi - da. Smeša n-propil polisulfi da ispoljava jaču citotoksičnu aktivnost na ćelijskim linijama mišjeg karcinoma kolona i melanoma i slabiju aktivnost na mMSC u poređenju sa efektom cisplatine.",
journal = "Serbian Journal of Experimental and Clinical Research",
title = "Antitumour effect of a mixture of n-propyl polysulfides In vitro, Antitumorski efekti smeše n-propil polisulfida in vitro",
volume = "20",
number = "4",
pages = "295-300",
doi = "10.1515/sjecr-2017-0069"
}

Đorđević, D. B., Milovanović, J., Jurisević, M., Stojanović, B., Cvetković, O., Pergal, M., Ristanović, E., Vojvodić, D., Simić, M., Manojlović, D., Milovanović, M.,& Arsenijević, N.. (2019). Antitumour effect of a mixture of n-propyl polysulfides In vitro. in Serbian Journal of Experimental and Clinical Research, 20(4), 295-300.
https://doi.org/10.1515/sjecr-2017-0069

Đorđević DB, Milovanović J, Jurisević M, Stojanović B, Cvetković O, Pergal M, Ristanović E, Vojvodić D, Simić M, Manojlović D, Milovanović M, Arsenijević N. Antitumour effect of a mixture of n-propyl polysulfides In vitro. in Serbian Journal of Experimental and Clinical Research. 2019;20(4):295-300.
doi:10.1515/sjecr-2017-0069 .

Đorđević, Dragana B., Milovanović, Jelena, Jurisević, Milena, Stojanović, Bojana, Cvetković, Olga, Pergal, Marija, Ristanović, Elizabeta, Vojvodić, Danilo, Simić, Miloš, Manojlović, Dragan, Milovanović, Marija, Arsenijević, Nebojsa, "Antitumour effect of a mixture of n-propyl polysulfides In vitro" in Serbian Journal of Experimental and Clinical Research, 20, no. 4 (2019):295-300,
https://doi.org/10.1515/sjecr-2017-0069 . .

TY  - JOUR
AU  - Konovalov, Bata
AU  - Zivkovic, Marija D.
AU  - Milovanovic, Jelena Z.
AU  - Đorđević, Dragana B.
AU  - Arsenijevic, Aleksandar N.
AU  - Vasic, Ivana R.
AU  - Janjić, Goran
AU  - Franich, Andjela
AU  - Manojlović, Dragan
AU  - Škrivanj, Sandra
AU  - Milovanovic, Marija Z.
AU  - Đuran, Miloš
AU  - Rajkovic, Snezana
PY  - 2018
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/2353
AB  - The synthesis, spectroscopic characterization, cytotoxic activity and DNA binding evaluation of seven new dinuclear platinum(ii) complexes Pt1-Pt7, with the general formula [{Pt(L)Cl}(2)(-1,5-nphe)](ClO4)(2) (1,5-nphe is 1,5-naphthyridine; while L is two ammines (Pt1) or one bidentate coordinated diamine: ethylenediamine (Pt2), (+/-)-1,2-propylenediamine (Pt3), trans-(+/-)-1,2-diaminocyclohexane (Pt4), 1,3-propylenediamine (Pt5), 2,2-dimethyl-1,3-propylenediamine (Pt6), and 1,3-pentanediamine (Pt7)), were reported. In vitro cytotoxic activity of these complexes was evaluated against three tumor cell lines, murine colon carcinoma (CT26), murine mammary carcinoma (4T1) and murine lung cancer (LLC1) and two normal cell lines, murine mesenchymal stem cells (MSC) and human fibroblast (MRC-5) cells. The results of the MTT assay indicate that all investigated complexes have almost no cytotoxic effects on 4T1 and very low cytotoxicity toward LLC1 cell lines. In contrast to the effects on LLC1 and 4T1 cells, complexes Pt1 and Pt2 had significant cytotoxic activity toward CT26 cells. Complex Pt1 had a much lower IC50 value for activity on CT26 cells compared with cisplatin. In comparison with cisplatin, all dinuclear Pt1-Pt7 complexes showed lower cytotoxicity toward normal MSC and MRC-5 cells. In order to measure the amount of platinum(ii) complexes taken up by the cells, we quantified the cellular platinum content using inductively coupled plasma mass spectrometry (ICP-QMS). Molecular docking studies performed to evaluate the potential binding mode of dinuclear platinum(ii) complexes Pt1-Pt7 and their aqua derivatives W1-W7, respectively, at the double stranded DNA showed that groove spanning and backbone tracking are the most stable binding modes.
PB  - Royal Soc Chemistry, Cambridge
T2  - Dalton Transactions
T1  - Synthesis, cytotoxic activity and DNA interaction studies of new dinuclear platinum(ii) complexes with an aromatic 1,5-naphthyridine bridging ligand: DNA binding mode of polynuclear platinum(ii) complexes in relation to the complex structure
VL  - 47
IS  - 42
SP  - 15091
EP  - 15102
DO  - 10.1039/c8dt01946k
ER  - 

@article{
author = "Konovalov, Bata and Zivkovic, Marija D. and Milovanovic, Jelena Z. and Đorđević, Dragana B. and Arsenijevic, Aleksandar N. and Vasic, Ivana R. and Janjić, Goran and Franich, Andjela and Manojlović, Dragan and Škrivanj, Sandra and Milovanovic, Marija Z. and Đuran, Miloš and Rajkovic, Snezana",
year = "2018",
abstract = "The synthesis, spectroscopic characterization, cytotoxic activity and DNA binding evaluation of seven new dinuclear platinum(ii) complexes Pt1-Pt7, with the general formula [{Pt(L)Cl}(2)(-1,5-nphe)](ClO4)(2) (1,5-nphe is 1,5-naphthyridine; while L is two ammines (Pt1) or one bidentate coordinated diamine: ethylenediamine (Pt2), (+/-)-1,2-propylenediamine (Pt3), trans-(+/-)-1,2-diaminocyclohexane (Pt4), 1,3-propylenediamine (Pt5), 2,2-dimethyl-1,3-propylenediamine (Pt6), and 1,3-pentanediamine (Pt7)), were reported. In vitro cytotoxic activity of these complexes was evaluated against three tumor cell lines, murine colon carcinoma (CT26), murine mammary carcinoma (4T1) and murine lung cancer (LLC1) and two normal cell lines, murine mesenchymal stem cells (MSC) and human fibroblast (MRC-5) cells. The results of the MTT assay indicate that all investigated complexes have almost no cytotoxic effects on 4T1 and very low cytotoxicity toward LLC1 cell lines. In contrast to the effects on LLC1 and 4T1 cells, complexes Pt1 and Pt2 had significant cytotoxic activity toward CT26 cells. Complex Pt1 had a much lower IC50 value for activity on CT26 cells compared with cisplatin. In comparison with cisplatin, all dinuclear Pt1-Pt7 complexes showed lower cytotoxicity toward normal MSC and MRC-5 cells. In order to measure the amount of platinum(ii) complexes taken up by the cells, we quantified the cellular platinum content using inductively coupled plasma mass spectrometry (ICP-QMS). Molecular docking studies performed to evaluate the potential binding mode of dinuclear platinum(ii) complexes Pt1-Pt7 and their aqua derivatives W1-W7, respectively, at the double stranded DNA showed that groove spanning and backbone tracking are the most stable binding modes.",
publisher = "Royal Soc Chemistry, Cambridge",
journal = "Dalton Transactions",
title = "Synthesis, cytotoxic activity and DNA interaction studies of new dinuclear platinum(ii) complexes with an aromatic 1,5-naphthyridine bridging ligand: DNA binding mode of polynuclear platinum(ii) complexes in relation to the complex structure",
volume = "47",
number = "42",
pages = "15091-15102",
doi = "10.1039/c8dt01946k"
}

Konovalov, B., Zivkovic, M. D., Milovanovic, J. Z., Đorđević, D. B., Arsenijevic, A. N., Vasic, I. R., Janjić, G., Franich, A., Manojlović, D., Škrivanj, S., Milovanovic, M. Z., Đuran, M.,& Rajkovic, S.. (2018). Synthesis, cytotoxic activity and DNA interaction studies of new dinuclear platinum(ii) complexes with an aromatic 1,5-naphthyridine bridging ligand: DNA binding mode of polynuclear platinum(ii) complexes in relation to the complex structure. in Dalton Transactions
Royal Soc Chemistry, Cambridge., 47(42), 15091-15102.
https://doi.org/10.1039/c8dt01946k

Konovalov B, Zivkovic MD, Milovanovic JZ, Đorđević DB, Arsenijevic AN, Vasic IR, Janjić G, Franich A, Manojlović D, Škrivanj S, Milovanovic MZ, Đuran M, Rajkovic S. Synthesis, cytotoxic activity and DNA interaction studies of new dinuclear platinum(ii) complexes with an aromatic 1,5-naphthyridine bridging ligand: DNA binding mode of polynuclear platinum(ii) complexes in relation to the complex structure. in Dalton Transactions. 2018;47(42):15091-15102.
doi:10.1039/c8dt01946k .

Konovalov, Bata, Zivkovic, Marija D., Milovanovic, Jelena Z., Đorđević, Dragana B., Arsenijevic, Aleksandar N., Vasic, Ivana R., Janjić, Goran, Franich, Andjela, Manojlović, Dragan, Škrivanj, Sandra, Milovanovic, Marija Z., Đuran, Miloš, Rajkovic, Snezana, "Synthesis, cytotoxic activity and DNA interaction studies of new dinuclear platinum(ii) complexes with an aromatic 1,5-naphthyridine bridging ligand: DNA binding mode of polynuclear platinum(ii) complexes in relation to the complex structure" in Dalton Transactions, 47, no. 42 (2018):15091-15102,
https://doi.org/10.1039/c8dt01946k . .