Intensive investigation for novel antiproliferative and cytotoxic effective chemical compounds is currently concentrated on structurally modified agents of natural or synthetic source. The selenium derivative of triorganotin compound, triphenyltin isoselenocyanate (TPT-NCSe) caused higher cytotoxicity in hormone sensitive MCF 7 (IC 50-250 nM) in comparison with triple-negative MDA-MB-231 breast carcinoma cell line (IC 50-450 nM) as determined by MTT assay. Measurement of DNA damage showed presence of crosslinks in both cell lines treated by increasing TPT-NCSe concentrations. This compound decreased mitochondrial membrane potential shown by JC-1 staining in a concentration-dependent manner in both cell lines. Activation of caspases-3/7 was observed in MDA-MB-231 cells and was significant only by concentrations causing significant level of crosslinks. On the other hand, migration assay revealed inhibitory effect of viability keeping 100 nM concentration of TPT-NCSe on migration of MDA-MB-231 cells. Our data has shown that this selenium containing triorganotin molecule exerts DNA damage-linked antineoplastic activity in breast carcinoma cell lines studied.

Biomedical Research Center Cancer Research Institute Slovak Academy of Sciences Dubravska cesta 9 845 05 Bratislava Slovak Republic

Department of Chemical Drugs Faculty of Pharmacy Masaryk University Palackého třída 1946 1 612 00 Brno Czech Republic

Institute of Experimental Endocrinology Biomedical Research Center Slovak Academy of Sciences Dubravska cesta 9 845 05 Bratislava Slovak Republic

Institute of Immunology Faculty of Medicine Comenius University Odborarske nam 14 811 08 Bratislava Slovak Republic

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Triphenyltin isoselenocyanate: a novel nuclear retinoid X receptor ligand with antiproliferative and cytotoxic properties in cell lines derived from human breast cancer