title: Enhancement of diallyl disulfide-induced apoptosis by inhibitors of MAPKs in human HepG2 hepatoma cells.
abstract: We examined the effects of diallyl disulfide (DADS), an oil-soluble organosulfur compound found in garlic, on human HepG2 hepatoma cells to better understand its effect on apoptosis and apoptosis-related genes. Our study has demonstrated that DADS affects cell proliferation activity and viability and elicits typical apoptotic morphologic changes (chromatic condensation and nuclear fragmentation) in human HepG2 hepatoma cells. Also, treatment with DADS induces a temporary increase in phosphorylated p38 MAPK (phospho-p38) and phosphorylated p42/44 MAPK (phospho-p42/p44) in a time- and concentration-dependent manner. Inhibition of activated/phosphorylated mitogen-activated protein kinase (MAPK) with phospho-p38 or phospho-p42/44 specific inhibitors, SB203580 or U0126, induces apoptosis without DADS treatment, indicating that at least the endogenous activated forms of p38 MAPK and p42/p44 MAPK markedly exert cytoprotective roles from cell apoptosis in the HepG2 hepatoma cells. Combined treatment with these inhibitors followed by DADS further enhances the DADS-induced apoptosis. Taken together, these results show that both DADS and the specific inhibitors of MAPKs could induce apoptosis in HepG2 hepatoma cells and that the MAPKs inhibitors further enhance the apoptotic effect in DADS-treated HepG2 hepatoma cells.
authors.affiliation: Research Institute for Molecular Pharmacology and Therapeutics, Central South University, Changsha, Hunan 410083, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wen
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Chen
authors.forename: Lingbo
authors.initials: L
authors.lastname: Shen
authors.forename: Gloria C
authors.initials: GC
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular; D004220:Disulfides / Q000494:pharmacology*; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D000498:Allyl Compounds; D004220:Disulfides; D004791:Enzyme Inhibitors; C028009:diallyl disulfide; D020928:Mitogen-Activated Protein Kinases