Suppression of Hepatitis B Virus X Protein-Mediated Tumorigenic Effects by Ursolic Acid

• Published in: Journal of agricultural and food chemistry 2011-03, Vol.59 (5), p.1713-1722
• Main Authors: Wu, Hong-Yin, Chang, Chi-I, Lin, Bo-Wei, Yu, Feng-Ling, Lin, Ping-Yuan, Hsu, Jue-Liang, Yen, Chia-Hung, Liao, Ming-Huei, Shih, Wen-Ling
• Format: Article
• Language: English
• Subjects: animal models; Animals; Antineoplastic Agents, Phytogenic - administration & dosage; apoptosis; Bioactive Constituents; Biological and medical sciences; Carcinoma, Hepatocellular; Cell Division - drug effects; Cell Line; Cell Line, Tumor; cell movement; Flavones - administration & dosage; Food industries; Fundamental and applied biological sciences. Psychology; Hepatitis B virus; hepatocytes; Hepatocytes - drug effects; Humans; immunoblotting; Liver Neoplasms - chemically induced; Liver Neoplasms - prevention & control; Mice; Mice, Nude; mitogen-activated protein kinase; Mitogen-Activated Protein Kinases - metabolism; Neoplasm Transplantation; neoplasms; oleanolic acid; Oleanolic Acid - administration & dosage; secretion; Signal Transduction; toxicity; Trans-Activators - antagonists & inhibitors; Trans-Activators - genetics; Trans-Activators - pharmacology; Transcriptional Activation - drug effects; Transfection; Triterpenes - administration & dosage; Ursolic Acid; Viral Regulatory and Accessory Proteins
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf1045624

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.