Resveratrol downregulates Akt/GSK and ERK signalling pathways in OVCAR-3 ovarian cancer cells

Daniele Vergara, Pasquale Simeone, Daniela Toraldo, Piero Del Boccio, Viviana Vergaro, Stefano Leporatti, Damiana Pieragostino, Andrea Tinelli, Stefania De Domenico, Saverio Alberti, Andrea Urbani, Michel Salzet, Angelo Santino, Michele Maffia

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1078-1087
Number of pages10
JournalMolecular BioSystems
Volume8
Issue number4
DOIs
Publication statusPublished - Mar 2012

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology

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