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 microg/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 G2/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.
Chiang
Lien-Chai
LC
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
Ng
Lean Teik
LT
Lin
I-Cheng
IC
Kuo
Po-Lin
PL
Lin
Chun-Ching
CC
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D053938:DNA Fragmentation; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016159:Tumor Suppressor Protein p53; D047310:Apigenin; D005472:Fluorouracil