title: Inhibitory effects of resveratrol on hepatitis B virus X protein-induced hepatocellular carcinoma.
abstract: Liver cancer occurs very frequently worldwide and hepatocellular carcinoma (HCC) accounts for more than 80% of total primary liver cancer cases. In this study, the anticarcinogenic effects of resveratrol against hepatitis B virus (HBV)-induced HCC were investigated by using HBV X-protein-overexpressing Huh7 (Huh7-HBx) human hepatoma cells. MTT assay showed that resveratrol decreased cell viability. Fluorescence-activated cell-sorter analysis showed that resveratrol induced G1 cell cycle arrest without increasing the sub-G1 phase cell population. Therefore, we evaluated its effect on regulation of cyclin D1, which is critically involved in G1/S transition. Resveratrol lowered cyclin D1 transcription. Western blot analysis of the effects of resveratrol on upstream cyclin D1 transcriptional signaling, extracellular signal-related kinase (ERK), p90RSK, Akt, and p70S6Krevealed inhibition of Akt but not the ERK signaling pathway. Collectively, the results indicate that resveratrol inhibits Huh7-HBx proliferation by decreasing cyclin D1 expression through blockade of Akt signaling. We investigated the anticarcinogenic effect and mechanism of resveratrol in xenograft model mice implanted with Huh7-HBx cells. Intraperitoneal resveratrol injection reduced tumor size in the mice. Expression of survivin was reduced, but cyclin D1 was not affected. The results demonstrate that resveratrol treatment may help manage HBV-induced HCC by regulating survivin.
authors.affiliation: BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.|Institute of Laboratory Animal Resources, Seoul National University, Seoul 08826, Korea.
authors.forename: Seungmo
authors.initials: S
authors.lastname: Park
authors.affiliation: College of Pharmacy, Seoul National University, Seoul 08826, Korea.
authors.forename: Jihae
authors.initials: J
authors.lastname: Lim
authors.affiliation: Advanced Institutes of Convergence Technology, Seoul National University, Seoul 08826, Korea.
authors.forename: Jong Rhan
authors.initials: JR
authors.lastname: Kim
authors.affiliation: BK21 PLUS Program for Creative Veterinary Science Research, Research Institute for Veterinary Science and College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
authors.forename: Seongbeom
authors.initials: S
authors.lastname: Cho
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D006515:Hepatitis B virus / Q000502:physiology; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000139:chemically induced; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology*; D000077022:Survivin; D015534:Trans-Activators / Q000494:pharmacology; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; C117749:Birc5 protein, mouse; C530105:Ccnd1 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D013267:Stilbenes; D000077022:Survivin; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D019938:Cyclin D1; D000077185:Resveratrol
keywords: Akt pathway; hepatitis B virus X protein; hepatocellular carcinoma; resveratrol; survivin