Involvement of p38 mitogen-activated protein kinase pathway in honokiol-induced apoptosis in a human hepatoma cell line (hepG2)

Background: Honokiol has been known to have antitumour activity. This study was conducted to evaluate the antiproliferative potential of honokiol against the hepG2 heptocellular cell line and its mechanism of action. Methods: hepG2 cells were treated with honokiol of 0-40 mu g/ml concentration. The cytotoxic effect of honokiol was determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptosis was evaluated by flow cytometry. Western blots were used to analyse the expression of various proteins (procaspase-9, procaspase-3, cleaved caspase-3, cytochrome c, Bcl-2, Bax, Bad, Bcl-X-L and p38). Results: Honokiol induced apoptosis with a decreased expression of procaspase-3 and -9 and an increased expression of active caspase-3. Exposure of hepG2 cells to honokiol resulted in the downregulation of Bcl-X-L and Bcl-2 expression and the release of mitochondrial cytochrome c to the cytosol. In addition, honokiol activated the p38 mitogen-activated protein kinase (MAPK) pathway, and the inhibition of this pathway by SB203580 reduced honokiol-induced apoptosis and activation of caspase-3. Conclusion: Honokiol induces apoptosis of hepG2 human hepatocellular carcinoma cells through activation of the p38 MAPK pathway, and, in turn, activation of caspase-3.