title: Overexpression of NAD(P)H: Quinone Oxidoreductase 1 Inhibits Hepatocellular Carcinoma Cell Proliferation and Induced Apoptosis by Activating AMPK/PGC-1α Pathway.
abstract: Hepatocellular carcinoma (HCC) is the most common lethal malignancy and a leading cause of malignancy-associated death in many countries, but mainly in Asia. Expression of the NAD(P)H:quinone oxidoreductase 1 (NQO1) protein is involved in the growth of various human cancers, including HCC. NQO1 is considered an inhibitor of cancers. The present study aimed to investigate the function and mechanism of NQO1 in HCC. In this study, we found that NQO1 overexpression decreased HCC cell SK-hep-1 and Hep3B cell proliferation and induced apoptosis. The apoptosis-associated gene Bax, Bcl-2, and caspase-3 expression was also measured, with western blot results showing that NQO1 overexpression inhibits Bcl-2 expression and promotes Bax and caspase-3 expression, whereas NQO1 silencing plays a contrasting role. In addition, NQO1 activated AMP-activated protein kinase (AMPK) and proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and the AMPK inhibitor compound C blocked NQO1-induced PGC-1α activation. Furthermore, the AMPK inhibitor compound C or PGC-1α siRNA partially abolished NQO1-induced cell apoptosis and proliferation inhibition in HCC cells. Taken together, our results demonstrate that NQO1 overexpression induces HCC cell apoptosis and proliferation inhibition through the AMPK/PGC-1α pathway.
authors.affiliation: 1 Department of Gastroenterology, Xi'an Central Hospital , Xi'an, China .
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 1 Department of Gastroenterology, Xi'an Central Hospital , Xi'an, China .
authors.forename: Kun
authors.initials: K
authors.lastname: Han
authors.affiliation: 2 Department of Gastroenterology, Affiliated Hospital of Yan'an University , Yan'an, China .
authors.forename: Dong-Hong
authors.initials: DH
authors.lastname: Yuan
authors.affiliation: 2 Department of Gastroenterology, Affiliated Hospital of Yan'an University , Yan'an, China .
authors.forename: Cun-Ying
authors.initials: CY
authors.lastname: Meng
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism* / Q000502:physiology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism*
chemical_list: C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D055372:AMP-Activated Protein Kinases
keywords: AMPK; NQO1; PGC-1α; apoptosis; hepatocellular carcinoma; proliferation