Properties of silibinin and of antioxidants against adriamycin cytotoxicity in a unicellular eukaryote, Tetrahymena thermophila

Abstract

Summary To elucidate the primary mechanism of adriamycin (ADR) cytotoxicity the properties of the flavonoid silibinin and of antioxidants against the cellular response to the anthracyclin drug were compared in Tetrahymena thermophila. Exponentially growing cultures were preincubated for 30 min with either silibinin, butylated hydroxyanisole (BHA) or a “cocktail” of superoxide dismutase (SOD), catalase and N-acetylcysteine (NAC), and then continuously exposed to these substances together with ADR (10 and 20 μg/ml). ADR administration alone resulted in a cell division arrest which was correlated with an inhibition of RNA synthesis and a minor and delayed reduction of protein synthesis. The inhibitory effects of ADR on growth and biomass production were completely prevented by silibinin (1 mg/ml). ADR uptake into silibinin-treated cells was proved by fluorescence microscopy. Antioxidants had no effect on ADR cytotoxicity. It is therefore suggested that redox processes are not the primary mechanism of ADR cytotoxicity in rapidly dividing cells and that cytoprotection by silibinin in this system is not due to its antioxidant properties. The data are rather in favour of ADR-DNA interactions and of a direct stimulatory effect of silibinin on RNA synthesis.