Apigenin Induces Apoptosis through a Mitochondria/Caspase-Pathway in Human Breast Cancer MDA-MB-453 Cells

In this study, we investigated the mechanistic role of the caspase cascade in extrinsic and intrinsic apoptosis induced by apigenin, which has been targeted as a candidate in the development of noncytotoxic anticancer medicines. Treatment with apigenin (1–100 µM) significantly inhibited the proliferation of MDA-MB-453 human breast cancer cells in a dose- and time-dependent manner with IC(50) values of 59.44 and 35.15 µM at 24 and 72 h, respectively. This inhibition resulted in the induction of apoptosis and the release of cytochrome c in cells exposed to apigenin at its 72 h IC(50). Subsequently, caspase-9, which acts in mitochondria-mediated apoptosis, was cleaved by apigenin. In addition, apigenin activated caspase-3, which functions downstream of caspase-9. The apigenin-induced activation of caspase-3 was accompanied by the cleavage of capases-6, -7, and -8. These results are supported by evidence showing that the activity patterns of caspases-3, -8, and -9 were similar. The present study supports the hypothesis that apigenin-induced apoptosis involves the activation of both the intrinsic and extrinsic apoptotic pathways.