Melanoma suppression by quercein is correlated with RIG-I and type I interferon signaling.

Abstract

Melanoma is a life-threatening cancer with limited treatments. Retinoic acid-inducible gene I (RIG-I) is a cytosolic pattern recognition receptor (PRR) crucial to RNA virus sensing, interferon production, and tumor suppression. Quercetin, a natural flavonoid, has particularly therapeutic interests to prevent and treat cancer, for its pharmacological effects against oxidant, inflammation, and angiogenesis. Quercetin was investigated for its anti-melanoma activity and potential mechanisms in this study. We found that quercetin inhibited mouse melanoma growth in vivo, and suppressed proliferation and promoted apoptosis of both B16 and A375 cells in vitro. Quercetin upregulated IFN-α and IFN-β expression through activating RIG-I promoter in B16 cells. The induction of IFN-α and IFN-β, which could be severely impaired by silencing RIG-I induced interferon stimulated genes (ISGs). Moreover, RIG-I likely amplifies antitumor effects by activating signal transduction and activator of transcription 1 (STAT1) in the IFN-JAK-STAT pathway in an autocrine and paracrine manner. Our study provided novel insights regarding biological and anti-proliferative activities of quercetin against melanoma, and we identified RIG-I as a potential target in anti-tumor therapies.

• Authors: Danhong Peng, Linjiao Chen, Yang Sun, Libo Sun, Qianqian Yin, Siyu Deng, Liman Niu, Fangzhou Lou, Zhikai Wang, Zhenyao Xu, Conghui Wang, Li Fan, Hong Wang, Honglin Wang
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 125 Pg. 109984 (May 2020) ISSN: 1950-6007 [Electronic] France
• PMID: 32066042 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.

Chemical References

• Antineoplastic Agents
• Interferon Type I
• Receptors, Immunologic
• Quercetin
• RIGI protein, human
• DEAD Box Protein 58

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (genetics)
• Cell Line, Tumor
• DEAD Box Protein 58 (genetics, metabolism)
• Disease Models, Animal
• Flow Cytometry
• Gene Expression Regulation, Neoplastic
• Humans
• Interferon Type I (metabolism)
• Melanoma (drug therapy, etiology, metabolism, pathology)
• Melanoma, Experimental
• Mice
• Promoter Regions, Genetic
• Quercetin (pharmacology)
• Receptors, Immunologic
• Signal Transduction (drug effects)
• Transcriptional Activation