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GRIM‑19‑mediated Stat3 activation is a determinant for resveratrol‑induced proliferation and cytotoxicity in cervical
Yong-Guang Li1, Hong-Juan Xia1, Jian-Ping Tao1
1Division of Cardiology, Sixth Hospital, Shanghai Jiao Tong University, State Key Discipline Division, Shanghai 200233, P.R. China.
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.
Insights
Resveratrol suppresses cervical cancer cell proliferation by inducing GRIM-19 protein, which inhibits Stat3 signaling. This study reveals a novel mechanism for resveratrol
Area of Science:
- Natural product chemistry
- Molecular oncology
- Cell signaling
Background:
- Resveratrol, a natural phenol found in grapes and berries, exhibits potential anticancer properties.
- Signal transducer and activator of transcription 3 (Stat3) activation is crucial in cancer development.
- The precise mechanisms by which resveratrol inhibits Stat3 signaling remain unclear.
Purpose of the Study:
- To investigate the effect of resveratrol on GRIM-19-Stat3 signaling in HeLa cervical cancer cells.
- To elucidate the role of GRIM-19 in mediating resveratrol's antitumor activity.
Main Methods:
- HeLa cells were treated with resveratrol.
- Western blotting was used to assess protein expression levels (p-Stat3, Stat3, GRIM-19).
- Cell viability was measured using MTT assays. GRIM-19 was modulated using short interfering RNAs (siRNAs).
Main Results:
- Resveratrol (100 µM) inhibited HeLa cell proliferation and Stat3 phosphorylation.
- Resveratrol treatment increased GRIM-19 protein expression.
- GRIM-19 overexpression suppressed Stat3 signaling, while GRIM-19 knockdown diminished resveratrol's effects on proliferation and Stat3 phosphorylation.
Conclusions:
- GRIM-19-Stat3 signaling is a key target pathway for resveratrol's antitumor effects in cervical cancer.
- Resveratrol exerts its antiproliferative effects by upregulating GRIM-19, leading to Stat3 pathway inhibition.
- This study provides novel insights into the molecular mechanisms of resveratrol's anticancer activity.
