title: SIRT1 sensitizes hepatocellular carcinoma cells expressing hepatitis B virus X protein to oxidative stress-induced apoptosis.
abstract: We previously showed that SIRT1 deacetylase inhibits proliferation of hepatocellular carcinoma cells expressing hepatitis B virus (HBV) X protein (HBX), by destabilization of β-catenin. Here, we report another role for SIRT1 in HBX-mediated resistance to oxidative stress. Ectopic expression and enhanced activity of SIRT1 sensitize Hep3B cells stably expressing HBX to oxidative stress-induced apoptosis. SIRT1 mutant analysis showed that nuclear localization of SIRT1 is not required for sensitization of oxidation-mediated apoptosis. Furthermore, ectopic expression of SIRT1 and treatment with resveratrol (a SIRT1 activator) attenuated JNK phosphorylation, which is a prerequisite for resistance to oxidative stress-induced apoptosis. Conversely, suppression of SIRT1 activity with nicotinamide inhibited the effect of resveratrol on JNK phosphorylation, leading to restoration of resistance to oxidation-induced apoptosis. Taken together, these results suggest that up-regulation of SIRT1 under oxidative stress may be a therapeutic strategy for treatment of hepatocellular carcinoma cells related to HBV through inhibition of JNK activation.
authors.affiliation: WCU, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Ratakorn
authors.initials: R
authors.lastname: Srisuttee
authors.forename: Sang Seok
authors.initials: SS
authors.lastname: Koh
authors.forename: Waraporn
authors.initials: W
authors.lastname: Malilas
authors.forename: Jeong
authors.initials: J
authors.lastname: Moon
authors.forename: Il-Rae
authors.initials: IR
authors.lastname: Cho
authors.forename: Byung Hak
authors.initials: BH
authors.lastname: Jhun
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Horio
authors.forename: Young-Hwa
authors.initials: YH
authors.lastname: Chung
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013267:Stilbenes / Q000494:pharmacology; D015534:Trans-Activators / Q000096:biosynthesis*; D015854:Up-Regulation; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D000975:Antioxidants; D034741:RNA, Small Interfering; D013267:Stilbenes; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D048670:MAP Kinase Kinase 4; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol