title: Resveratrol downregulates Akt/GSK and ERK signalling pathways in OVCAR-3 ovarian cancer cells.
abstract: Phytochemicals constitute a heterogeneous group of substances with an evident role in human health. Their properties on cancer initiation, promotion and progression are well documented. Particular attention is now devoted to better understand the molecular basis of their anticancer action. In the present work, we studied the effect of resveratrol on the ovarian cancer cell line OVCAR-3 by a proteomic approach. Our findings demonstrate that resveratrol down-regulates the protein cyclin D1 and, in a concentration dependent manner, the phosphorylation levels of protein kinase B (Akt) and glycogen synthase kinase-3β (GSK-3β). The dephosphorylation of these kinases could be responsible for the decreased cyclin D1 levels observed after treatment. We also showed that resveratrol reduces phosphorylation levels of the extracellular signal-regulated kinase (ERK) 1/2. Chemical inhibitors of phosphatidylinositol 3-kinase (PI3K) and ERK both increased the in vitro therapeutic efficacy of resveratrol. Moreover, resveratrol had an inhibitory effect on the AKT phosphorylation in cultured cells derived from the ascites of ovarian cancer patients and in a panel of human cancer cell lines. Thus, resveratrol shows antitumor activity in human ovarian cancer cell lines targeting signalling pathway involved in cell proliferation and drug-resistance.
authors.affiliation: Laboratory of General Physiology, Department of Biological and Environmental Sciences and Technologies, University of Salento, via Monteroni 73100, Lecce, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Vergara
authors.forename: Pasquale
authors.initials: P
authors.lastname: Simeone
authors.forename: Daniela
authors.initials: D
authors.lastname: Toraldo
authors.forename: Piero
authors.initials: P
authors.lastname: Del Boccio
authors.forename: Viviana
authors.initials: V
authors.lastname: Vergaro
authors.forename: Stefano
authors.initials: S
authors.lastname: Leporatti
authors.forename: Damiana
authors.initials: D
authors.lastname: Pieragostino
authors.forename: Andrea
authors.initials: A
authors.lastname: Tinelli
authors.forename: Stefania
authors.initials: S
authors.lastname: De Domenico
authors.forename: Saverio
authors.initials: S
authors.lastname: Alberti
authors.forename: Andrea
authors.initials: A
authors.lastname: Urbani
authors.forename: Michel
authors.initials: M
authors.lastname: Salzet
authors.forename: Angelo
authors.initials: A
authors.lastname: Santino
authors.forename: Michele
authors.initials: M
authors.lastname: Maffia
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D018613:Microscopy, Confocal; D010051:Ovarian Neoplasms / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D040901:Proteomics / Q000379:methods; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C530104:CCND1 protein, human; D013267:Stilbenes; D019938:Cyclin D1; D019869:Phosphatidylinositol 3-Kinases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D038362:Glycogen Synthase Kinase 3; D000077185:Resveratrol