Quercetin inhibits the metabolism of arachidonic acid by inhibiting the activity of CYP3A4, thereby inhibiting the progression of breast cancer

Molecular Medicine

Research Article

Wan Wu¹  Yuanli Kuang¹  Qianmei Fu²  Bing Peng³  Huaming Tang³ 

[1] Department of General Surgery, Chongqing Kaizhou District People’s Hospital, 400700, Chongqing, People’s Republic of China;Department of Oncology, Chongqing Kaizhou District People’s Hospital, No. 8, Ankang Road, Hanfeng Street, Kaizhou District, 400700, Chongqing, People’s Republic of China;Department of Pancreatic Surgery, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Wuhou District, 610000, Chengdu, Sichuan Province, People’s Republic of China;

关键词: Saffron;    Quercetin;    Breast carcinoma;    Cytochrome P450 family 3 subfamily A member 4;    Arachidonic acid;    Epoxyeicosatrienoic acids;   

DOI  :  10.1186/s10020-023-00720-8

 received in 2023-03-06, accepted in 2023-08-25,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundRecent years have witnessed impressive growth in applying natural medicine in tumor treatment. Saffron is reported to elicit an inhibitory property against BC. Herein, we sought to explore the specific components and mechanistic basis of saffron’s anti-breast carcinoma (BC) function.MethodsBioinformatics analysis was employed to analyze saffron components' anti-BC activity and screen the corresponding target genes involved in BC. Then, the roles of the main saffron ingredient quercetin in the activity of BC cells were examined using CCK-8, MTS, flow cytometry, colony formation, Transwell, and Gelatin zymogram assays. Additionally, the interactions among Quercetin, EET, and Stat3 were assessed by immunofluorescence and Western blot, and LC–MS/MS determined the levels of AA, EETs, and CYP3A. Finally, BC xenograft mouse models were established to verify the anti-BC function of Quercetin in vivo.ResultsQuercetin, the main active component of saffron, inhibited BC progression. Quercetin suppressed BC cell growth, migration, and invasion and inhibited CYP3A4 expression and activity in BC. Mechanistically, Quercetin down-regulated CYP3A4 to block the nuclear translocation of Stat3 by decreasing the metabolization of AA to EETs, thereby alleviating BC. Moreover, exogenously added EETs counteracted the anti-tumor effect of Quercetin on BC. Quercetin also inhibited the tumor growth of tumor-bearing nude mice.ConclusionQuercetin could inhibit the activity of CYP3A to down-regulate AA metabolites EETs, consequently hampering p-Stat3 and nuclear translocation, thus impeding BC development.

【 授权许可】

CC BY   
© The Feinstein Institute for Medical Research 2023

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