title: GRIM‑19‑mediated Stat3 activation is a determinant for resveratrol‑induced proliferation and cytotoxicity in cervical tumor‑derived 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 GRIM‑19‑Stat3 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 p‑Stat3, Stat3, GRIM‑19 and β‑actin. 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 retinoid‑IFN‑induced mortality 19 (GRIM‑19) protein. Overexpression of GRIM‑19 suppressed the Stat3 signaling pathway in HeLa cells. The Stat3 signaling pathway was activated following the downregulation of GRIM‑19 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 GRIM‑19‑Stat3 signaling as a target of resveratrol, and further elucidates the mechanisms underlying the antitumor activity of resveratrol.
authors.affiliation: Division of Cardiology, Sixth Hospital, Shanghai Jiao Tong University, State Key Discipline Division, Shanghai 200233, P.R. China.
authors.forename: Yong-Guang
authors.initials: YG
authors.lastname: Li
authors.affiliation: Division of Cardiology, Sixth Hospital, Shanghai Jiao Tong University, State Key Discipline Division, Shanghai 200233, P.R. China.
authors.forename: Hong-Juan
authors.initials: HJ
authors.lastname: Xia
authors.affiliation: Division of Cardiology, Sixth Hospital, Shanghai Jiao Tong University, State Key Discipline Division, Shanghai 200233, P.R. China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Tao
authors.affiliation: Division of Cardiology, Sixth Hospital, Shanghai Jiao Tong University, State Key Discipline Division, Shanghai 200233, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Xin
authors.affiliation: Division of Cardiology, Sixth Hospital, Shanghai Jiao Tong University, State Key Discipline Division, Shanghai 200233, P.R. China.
authors.forename: Ming-Ya
authors.initials: MY
authors.lastname: Liu
authors.affiliation: Division of Cardiology, Sixth Hospital, Shanghai Jiao Tong University, State Key Discipline Division, Shanghai 200233, P.R. China.
authors.forename: Jing-Bo
authors.initials: JB
authors.lastname: Li
authors.affiliation: Division of Cardiology, Sixth Hospital, Shanghai Jiao Tong University, State Key Discipline Division, Shanghai 200233, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Division of Cardiology, Sixth Hospital, Shanghai Jiao Tong University, State Key Discipline Division, Shanghai 200233, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wei
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006367:HeLa Cells; D006801:Humans; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D000077185:Resveratrol; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000633:toxicity*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D056744:Cyclin B1; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; D013267:Stilbenes; D042461:Vascular Endothelial Growth Factor A; D009247:NADH, NADPH Oxidoreductases; C439057:NDUFA13 protein, human; D000077185:Resveratrol