Anthocyanins are a class of
flavonoids, widely spread throughout the plant kingdom, that exhibit important
anti-oxidant and anti-inflammatory actions as well as chemotherapeutic effects. However, little is known concerning the molecular mechanisms by which these activities are exerted. In this study, we investigated the
anthocyanins isolated from Vitis coignetiae Pulliat for their potential anti-proliferative and apoptotic effects on human
leukemia U937 cells. It was found that these
anthocyanins inhibit cell viability and induce apoptotic cell death of U937 cells in a dose-dependent manner, as measured by hemocytometer counts, by alteration in the mitochondrial membrane potential, by increases in sub-G1 populations and by
DNA ladder formation. Apoptosis of U937 cells by
anthocyanins was associated with modulation of expression of Bcl-2 and IAP family members. Consequently,
anthocyanin treatment induced proteolytic activation of
caspase-3, -8 and -9, and a concomitant degradation of
poly(ADP-ribose) polymerase. However,
anthocyanin-induced growth inhibition and apoptosis were significantly attenuated in Bcl-2 overexpressing U937 cells. Furthermore,
z-DEVD-fmk, a
caspase-3 specific inhibitor, blocked apoptosis and increased the survival of
anthocyanin-treated U937 cells. Taken together, these results show that Bcl-2 and
caspases are key regulators of apoptosis in response to
anthocyanins in human
leukemia U937 cells.