title: Vitexin suppresses autophagy to induce apoptosis in hepatocellular carcinoma via activation of the JNK signaling pathway.
abstract: Vitexin, a flavonoids compound, is known to exhibit broad anti-oxidative, anti-inflammatory, analgesic, and antitumor activity in many cancer xenograft models and cell lines. The purpose of this study was to investigate the antitumor effects and underlying mechanisms of vitexin on hepatocellular carcinoma. In this study, we found that vitexin suppressed the viability of HCC cell lines (SK-Hep1 and Hepa1-6 cells) significantly. Vitexin showed cytotoxic effects against HCC cell lines in vitro by inducing apoptosis and inhibiting autophagy. Vitexin induced apoptosis in a concentration-dependent manner, and caused up-regulations of Caspase-3, Cleave Caspase-3, and a down-regulation of Bcl-2. The expression of autophagy-related protein LC3 II was significantly decreased after vitexin treatment. Moreover, western blot analysis presented that vitexin markedly up-regulated the levels of p-JNK and down-regulated the levels of p-Erk1/2 in SK-Hep1 cells and Hepa1-6 cells. Cotreatment with JNK inhibitor SP600125, we demonstrated that apoptosis induced by vitexin was suppressed, while the inhibition of autophagy by vitexin was reversed. The results of colony formation assay and mouse model confirmed the growth inhibition role of vitexin on HCC in vitro and in vivo. In conclusion, vitexin inhibits HCC growth by way of apoptosis induction and autophagy suppression, both of which are through JNK MAPK pathway. Therefore, vitexin could be regarded as a potent therapeutic agent for the treatment of HCC.
authors: First Central Clinical College, Tianjin Medical University, Tianjin 300192, P.R. China.
authors: Jin-Dan
authors: JD
authors: He
authors: First Central Clinical College, Tianjin Medical University, Tianjin 300192, P.R. China.
authors: Zhen
authors: Z
authors: Wang
authors: First Central Clinical College, Tianjin Medical University, Tianjin 300192, P.R. China.|Department of General Surgery, The People's Hospital of Jiaozuo City, Jiaozuo 454002, P.R. China.
authors: Shi-Peng
authors: SP
authors: Li
authors: First Central Clinical College, Tianjin Medical University, Tianjin 300192, P.R. China.
authors: Yan-Jie
authors: YJ
authors: Xu
authors: First Central Clinical College, Tianjin Medical University, Tianjin 300192, P.R. China.
authors: Yao
authors: Y
authors: Yu
authors: First Central Clinical College, Tianjin Medical University, Tianjin 300192, P.R. China.
authors: Yi-Jie
authors: YJ
authors: Ding
authors: Department of Anesthesiology, Tianjin First Central Hospital, Tianjin 300192, P.R. China.
authors: Wen-Li
authors: WL
authors: Yu
authors: Laboratory of Immunology and Inflammation, Department of Immunology, Key Laboratory of Immune Microenvironment and Diseases of Educational Ministry of China, Basic Medical College, Tianjin Medical University, Tianjin 300070, P.R. China.
authors: Rong-Xin
authors: RX
authors: Zhang
authors: First Central Clinical College, Tianjin Medical University, Tianjin 300192, P.R. China.|Department of Liver Transplantation, Oriental Organ Transplant Center of Tianjin First Central Hospital, Key Laboratory of Organ Transplantation of Tianjin, Tianjin 300192, P.R. China.
authors: Hai-Ming
authors: HM
authors: Zhang
authors: Department of Anesthesiology, Tianjin First Central Hospital, Tianjin 300192, P.R. China.|First Central Clinical College, Tianjin Medical University, Tianjin 300192, P.R. China.
authors: Hong-Yin
authors: HY
authors: Du
mesh_terms: D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D000071183:Autophagy-Related Proteins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008810:Mice, Inbred C57BL; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071183:Autophagy-Related Proteins; D047310:Apigenin; C032731:vitexin; D053148:Caspase 3
keywords: JNK signaling; apoptosis; autophagy; hepatocellular carcinoma; vitexin