title: Resveratrol exerts its antiproliferative effect on HepG2 hepatocellular carcinoma cells, by inducing cell cycle arrest, and NOS activation.
abstract: The stilbene resveratrol exerts antiproliferative and proapoptotic actions on a number of different cancer cell lines, through diverse mechanisms, including antioxidant effects, enzyme, growth factor and hormone receptor binding, and nucleic acid direct or indirect interactions. Although resveratrol accumulates in the liver, its effect on hepatocellular carcinoma has not been extensively studied. We have used the human hepatocyte-derived cancer cell line HepG2 to address the possible action of resveratrol on cell growth and to examine some possible mechanisms of action. Our results indicate that the stilbene inhibits potently cell proliferation, reduces the production of reactive oxygen species and induces apoptosis, through cell cycle arrest in G1 and G2/M phases. Furthermore it modulates the NO/NOS system, by increasing iNOS and eNOS expression, NOS activity and NO production. Inhibition of NOS enzymes attenuates its antiproliferative effect. These data could be of value in possible prevention or adjuvant treatment of hepatocellular carcinoma, through an increased consumption of resveratrol-rich foods and beverages.
authors.affiliation: Laboratories of Gastroenterology, University of Crete School of Medicine, Heraklion, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Notas
authors.forename: Artemissia-Phoebe
authors.initials: AP
authors.lastname: Nifli
authors.forename: Marilena
authors.initials: M
authors.lastname: Kampa
authors.forename: Joseph
authors.initials: J
authors.lastname: Vercauteren
authors.forename: Elias
authors.initials: E
authors.lastname: Kouroumalis
authors.forename: Elias
authors.initials: E
authors.lastname: Castanas
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D016193:G1 Phase; D016195:G2 Phase; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017382:Reactive Oxygen Species; D013267:Stilbenes; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000077185:Resveratrol