Activin has a wide variety of biological functions, including the regulation of cell proliferation and inhibition of tumor cells. We have studied whether activin regulates apoptosis by investigating the effects of activin A on cell proliferation, cell cycle, apoptosis, apoptosis-related gene expression, and caspase activity in SNU-16 cells. Activin A significantly inhibited DNA synthesis and growth suppression in a time-dependent manner in SNU-16 cells. Apoptosis fraction was increased at cell cycle with an accompanying DNA fragmentation. Activin A resulted in a significant time-dependent decrease in Bcl-2 mRNA levels and increase in caspase-3 mRNA levels in SNU-16 cells. No significant difference was observed in Bax mRNA levels. Exposure of cells to activin A induced caspase-3, -8 and -9 activation in SNU-16 cells. Furthermore, co-treatment of activin with the pan-caspase inhibitor Z-VAD-FMK, caspase-3 inhibitor Z-DEVE-FMK, caspase-8 inhibitor Z-IETD-FMK, and caspase-9-inhibitor Z-LEHD-FMK blocked apoptosis of SNU-16 cells. Taken together, our results revealed that activin inhibits the growth of SNU-16 cells by inducing apoptosis through caspase activation.

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