Antitumour effect of a mixture of n-propyl polysulfides In vitro

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.