Anti-proliferative effect of apigenin and its apoptotic induction in human Hep G2 cells

Apigenin, a common dietary flavonoid abundantly present in fruits and vegetables, is believed to possess preventive and therapeutic potential against cancers. In this study, the anti-hepatoma property of apigenin was evaluated on three different human hapatoma cells, namely Hep G2, Hep 3B, and PLC/PRF/5 cells. Results showed that apigenin exhibited a significant growth inhibition against the three selected hepatoma cell lines but not the normal murine liver BNL CL.2 cells. Interestingly, it was shown to possess a similar potency as a commercial anti-hepatoma agent 5-flurouracil (5-FU: positive control) against Hep G2 cells, with IC50 value of 8.02 +/- 1.30 mu g/ml. Therefore, we conducted our Study further to investigate the cellular mechanism of apigenin effect on Hep G2 cell death. Using DNA ladder and flow cytometric analysis, apigenin was found to induce apoptosis in Hep G2 cells. It also increased the accumulation of p53 and further enhanced the level of p21/WAF1. Together, it was shown that the apoptosis induced by apigenin in Hep G2 cells was possibly mediated through the p53-dependent pathway and the induction of p21 expression, which was probably associated with the cell cycle arrest in G(2)/M phase. The present study concludes that the anti-hepatoma activity of apigenin is as effective as 5-FU and its apoptotic mechanism might be mediated through the p53-dependent pathway and the induction of p21 expression. (c) 2005 Elsevier Ireland Ltd. All rights reserved.