title: Suppression of hepatitis B virus x protein-mediated tumorigenic effects by ursolic Acid.
abstract: This study investigated the potential effects of natural products ursolic acid (UA) and oleanolic acid (OA) against HBx-mediated tumorigenic activities in vitro and in vivo. HBx transactivated Sp-1 and Smad 3/4 in Huh7 and FL83B hepatocytes and induced cell migration of Huh7 and HepG2. HBx also induced MMP-3 secretion in Huh7 and acted against TGF-β-induced apoptosis in Hep3B. UA almost completely blocked the HBx-mediated effects, while OA had a partial inhibitive effect. Utilization of specific MAPK inhibitors and immunoblotting demonstrated that UA selectively activated MAPK signaling in certain tested cells. Preintraperitoneal injection of UA fully prevented the tumor growth of HBV-containing 2.2.15 cells, while OA-treated mice had smaller tumors than the control group. Our results suggested that UA possesses a hepatoprotective ability and illustrated the evident effects against HBx-mediated tumorigenic activities without toxicity in a mouse model.
authors.affiliation: Graduate Institute of Biotechnology, National Pingtung University of Science and Technology, 1, Shuefu Rd., Neipu, Pingtung, 91201, Taiwan.
authors.forename: Hong-Yin
authors.initials: HY
authors.lastname: Wu
authors.forename: Chi-I
authors.initials: CI
authors.lastname: Chang
authors.forename: Bo-Wei
authors.initials: BW
authors.lastname: Lin
authors.forename: Feng-Ling
authors.initials: FL
authors.lastname: Yu
authors.forename: Ping-Yuan
authors.initials: PY
authors.lastname: Lin
authors.forename: Jue-Liang
authors.initials: JL
authors.lastname: Hsu
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Yen
authors.forename: Ming-Huei
authors.initials: MH
authors.lastname: Liao
authors.forename: Wen-Ling
authors.initials: WL
authors.lastname: Shih
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D047309:Flavones / Q000008:administration & dosage; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D008819:Mice, Nude; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009368:Neoplasm Transplantation; D009828:Oleanolic Acid / Q000008:administration & dosage; D015398:Signal Transduction; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014315:Triterpenes / Q000008:administration & dosage*; D054334:Viral Regulatory and Accessory Proteins; D000097245:Ursolic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D047309:Flavones; D020928:Mitogen-Activated Protein Kinases; D009828:Oleanolic Acid; D015534:Trans-Activators; D014315:Triterpenes; D054334:Viral Regulatory and Accessory Proteins; D000097245:Ursolic Acid; C057628:hepatitis B virus X protein; C008661:nobiletin; C059006:tangeretin