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Induction of apoptosis by piceatannol in human leukemic U937 cells through down-regulation of Bcl-2 and activation of caspases.

Piceatannol is a polyphenol that is found in abundant quantities in grapes and wine. Although recent experimental data revealed the proapoptotic potency of piceatannol, the molecular mechanisms underlying the anti-leukemic activity have not yet been studied in detail. This study examined the effects of piceatannol on the growth of the human leukemia cell line U937. The results showed that piceatannol inhibits the viability of U937 cells by inducing apoptosis, as evidenced by the formation of apoptotic bodies, DNA fragmentation and the accumulation of the sub-G1 phase. RT-PCR and immunoblotting data showed that treating the cells with piceatannol caused the down-regulation of anti-apoptotic Bcl-2 and cIAP-2 expression. Piceatannol-induced apoptosis was also associated with the proteolytic activation of caspase-3, and the degradation/cleavage of poly (ADP-ribose) polymerase protein. z-DEVD-fmk, a caspase-3-specific inhibitor, blocked the activation of caspase-3 and increased the survival of the piceatannol-treated U937 cells, suggesting that caspase-3 activation is essential for piceatannol-induced apoptosis.