title: Metformin inhibits growth of hepatocellular carcinoma cells by inducing apoptosis via mitochondrion-mediated pathway.
abstract: Recently, population-based studies of type 2 diabetes patients have provided evidence that metformin treatment is associated with a reduced cancer incidence and mortality, but its mode of action remains unclear. Here we report effects of metformin on hepatocellular carcinoma (HCC) Hep-G2 cells and details of molecular mechanisms of metformin activity. Our research indicates that metformin displays anticancer activity against HCC through inhibition of the mTOR translational pathway in an AMPK-independent manner, leading to G1 arrest in the cell-cycle and subsequent cell apoptosis through the mitochondrion-dependent pathway. Furthermore, we showed that metformin strongly attenuated colony formation and dramatically inhibited Hep-G2 tumor growth in vivo. In conclusion, our studies suggested that metformin might have potential as a cytotoxic drug in the prevention and treatment of HCC.
authors.affiliation: Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Xiamen, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xiong
authors.forename: Qing-Jun
authors.initials: QJ
authors.lastname: Lu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Guo-Yang
authors.initials: GY
authors.lastname: Wu
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008687:Metformin / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D008687:Metformin; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D000091162:AMP-Activated Protein Kinase Kinases