title: Pterostilbene inhibits hepatocellular carcinoma through p53/SOD2/ROS-mediated mitochondrial apoptosis.
abstract: Hepatocellular carcinoma (HCC) is one of the most common malignancies and the second cause of cancer-related deaths around the world. Pterostilbene (PTE), is a natural analog of resveratrol, possessing diverse pharmacological activities. In the present study, we aimed to examine the effect of PTE on tumor growth in mouse models of HCC and to elucidate the possible molecular mechanism in vivo and in vitro. We showed that PTE dose-dependently suppressed tumor growth in mice induced by diethylnitrosamine plus carbon tetrachloride, as evidenced by a decrease in the number of tumors and in the maximum size of the tumors. PTE concentration-dependently inhibited cell viability and proliferation in HepG2 cells. PTE increased caspase-3 activities and apoptosis in liver tumor tissues and cells, indicating the activation of the mitochondrial apoptotic pathway. PFTα, superoxide dismutase 2 (SOD2) lentivirus and N-acetylcysteine (NAC) significantly inhibited PTE-induced inhibition of tumor growth and cell proliferation and increase in apoptosis. PTE dose-dependently increased reactive oxygen species (ROS) levels both in liver tumor tissues and cells, which were inhibited by PFTα, SOD2 lentivirus and NAC. PTE resulted in a significant decrease in SOD2 expression in liver tumor tissues and cells, which were inhibited by PFTα, but not NAC, indicating that PTE-induced ROS generation was attributed to p53-mediated downregulation of SOD2. Collectively, PTE increased p53 expression, decreased SOD2 expression, and resulted in an increase in the ROS levels and the activation of the mitochondrial apoptotic pathway, leading to inhibition of tumor growth and cell proliferation. These data demonstrated that the p53/SOD2/ROS pathway is critical for PTE-mediated inhibition of tumor growth and HCC cell proliferation.
authors.affiliation: Department of Hepatology, Xi'an No. 8 Hospital, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Liying
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of General Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Tan
authors.affiliation: Department of Hematology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, P.R. China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008810:Mice, Inbred C57BL; D008928:Mitochondria; D017382:Reactive Oxygen Species / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000099156:Superoxide Dismutase 2
chemical_list: D017382:Reactive Oxygen Species; D013267:Stilbenes; D013482:Superoxide Dismutase; D016159:Tumor Suppressor Protein p53; D000099156:Superoxide Dismutase 2; C495901:TP53 protein, human; C107773:pterostilbene