INDUCTION OF APOPTOSIS BY SODIUM-BUTYRATE IN THE HUMAN Y-79 RETINOBLASTOMA CELL-LINE

The mode of cell death induced in the Y-79 human retinoblastoma cell l ine by sodium butyrate (SB), a short-chain fatty acid with potent inhi bitory effects on the growth of many transformed cell Lines, was inves tigated by fluorescence and transmission electron microscopy, agarose gel electrophoresis, and metabolic studies. While SB (<1 mM) resulted in marked morphological differentiation, higher concentrations (1-4 mM ) induced predominantly apoptotic involution in Y-79 in a concentratio n-dependent fashion after a latent period of 24 h. Dying cells display ed the characteristic morphology of apoptosis accompanied by DNA ladde ring with agarose gel electrophoresis. Extensive cell necrosis was app arent with 0.5 M SB. Induction of apoptosis and DNA laddering by SB wa s reduced by putative inhibitors of RNA and protein synthesis, but not putative endonuclease inhibitors. These results are important for und erstanding the mode of action of sodium butyrate as a potential cancer chemotherapeutic agent.