GRIM19mediated Stat3 activation is a determinant for resveratrolinduced proliferation and cytotoxicity in cervical tumorderived cell lines

Abstract

Resveratrol is a natural phenol, produced from red grapes, berries and peanuts. Previous studies have suggested that resveratrol exerts anticancer effects. Activation of the signal transducer and activator of transcription 3 (Stat3) is important in cancer. However, the mechanisms by which resveratrol suppresses the Stat3 signaling pathway remain to be elucidated. The aim of the present study was to investigate the effects of resveratrol on GRIM19Stat3 signaling in HeLa cells, derived from a cervical tumor. HeLa cells were divided into experimental groups and treated with resveratrol. Western blotting was used to analyze the expression levels of pStat3, Stat3, GRIM19 and βactin. Cell viability was determined using an MTT assay. The results showed that 100 μM resveratrol suppressed the proliferation and Stat3 phosphorylation in HeLa cells, and induced the expression of the gene associated with retinoidIFNinduced mortality 19 (GRIM19) protein. Overexpression of GRIM19 suppressed the Stat3 signaling pathway in HeLa cells. The Stat3 signaling pathway was activated following the downregulation of GRIM19 expression using short interfering RNAs (siRNAs). Resveratrol suppressed cell proliferation, however, this effect was decreased through the use of siRNAs. The suppression of Stat3 phosphorylation by resveratrol decreased following treatment with siRNAs. To the best of our knowledge, the present study is among the first to identify GRIM19Stat3 signaling as a target of resveratrol, and further elucidates the mechanisms underlying the antitumor activity of resveratrol.