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 microg/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.


CONCLUSIONS
Honokiol induces apoptosis of hepG2 human hepatocellular carcinoma cells through activation of the p38 MAPK pathway, and, in turn, activation of caspase-3.
Key Laboratory of Combined Multi-Organ Transplantation, Department of Hepatobiliary Pancreatic Surgery, Ministry of Public Health, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Junfang
J
Deng
Yigang
Y
Qian
Lei
L
Geng
Jie
J
Chen
Xiaohui
X
Wang
Haiyang
H
Xie
Sheng
S
Yan
Guoping
G
Jiang
Lin
L
Zhou
Shusen
S
Zheng
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D007093:Imidazoles; D017705:Lignans / Q000494:pharmacology*; D011725:Pyridines; D015398:Signal Transduction / Q000502:physiology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000498:Allyl Compounds; D010636:Phenols
D001713:Biphenyl Compounds; D020169:Caspases; D007093:Imidazoles; D017705:Lignans; D011725:Pyridines; D013778:Tetrazolium Salts; D013844:Thiazoles; D048051:p38 Mitogen-Activated Protein Kinases; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C022616:thiazolyl blue; C093642:SB 203580