Aim: To investigate the mechanism by which galangin, a polyphenolic compound derived from medicinal herbs, induces autophagy of HepG2 cells. Methods: The MTT [3-(4,5-dimethyl-thiazol-2-yl)2,5-diphenyl-tetrazolium bromide] assay was used to measure cell viability. Apoptosis was evaluated by TUNEL assay with flow cytometry, and PARP cleavage was detected by Western blotting. Autophagy was measured by fluorescence microscopy and transmission electron microscopy. Protein expressions were detected by Western blotting. Pifithrin-α was used for pretreatment and siRNA was used to knock down p53 expression to explore the pathway mediated by galangin in HepG2 cells. Furthermore, Hep3B cells were used to express the exogenous wild-type p53. Results: Galangin treatment inhibited cell proliferation and induced autophagy (130 µmol/l) and apoptosis (370 µmol/l). In particular, galangin treatment in HepG2 cells caused (1) an accumulation of autophagosomes, (2) elevated levels of microtubule-associated protein light chain 3, and (3) an increased percentage of cells with vacuoles. p53 expression was also increased. The galangin-induced autophagy was attenuated by the inhibition of p53 in HepG2 cells, and overexpression of p53 in Hep3B cells restored the galangin-induced higher percentage of cells with vacuoles to normal level. Conclusion: Our results indicate that galangin not only induced apoptosis but also prompted cell autophagy in different concentrations. Galangin mediates autophagy through a p53-dependent pathway in HepG2 cells. Our findings may help in the discovery of a chemotherapeutic drug with the novel pattern of inhibiting cell proliferation for the treatment of hepatocellular carcinoma cells.

Keywords:
Galangin, Hepatocellular carcinoma, Autophagy, p53
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© 2012 S. Karger AG, Basel
2012
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