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In addition, the flavonoids kaempferol and quercetin are natural products that directly bind NR4A1 and significantly repress the intrinsic NR4A1-dependent transcriptional activity in human endometriotic epithelial and stromal cells and Ishikawa endometrial cancer cells. NR4A1 knockdown and inhibition of NR4A1 by kaempferol and quercetin suppressed proliferation of human endometriotic epithelial cells and Ishikawa cells by inhibiting epidermal growth factor receptor\/c-Myc\/survivin-mediated growth-promoting and survival pathways, The mammalian target of rapamycin (mTOR) signaling and \u03b1SMA\/CTGF\/COL1A1\/FN-mediated fibrosis signaling but increasing Thioredoxin domain Containing 5\/SESN2-mediated oxidative\/estrogen receptors stress signaling. In human endometriotic stromal cells, NR4A1 knockdown and inhibition of NR4A1 by kaempferol and quercetin primarily inhibited mTOR signaling by suppressing proliferation of human endometrial stromal cells. In addition, kaempferol and quercetin treatment also effectively suppressed the growth of endometriotic lesions in mice with endometriosis compared with the vehicle without any body weight changes. Therefore, kaempferol and quercetin are NR4A1 antagonists with potential as nutritional therapy for endometriosis.<\/jats:p>","DOI":"10.1210\/endocr\/bqad133","type":"journal-article","created":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T20:17:17Z","timestamp":1693340237000},"source":"Crossref","is-referenced-by-count":38,"title":["Flavonoids Quercetin and Kaempferol Are NR4A1 Antagonists and Suppress Endometriosis in Female Mice"],"prefix":"10.1210","volume":"164","author":[{"given":"Lei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Veterinary Physiology and Pharmacology, Texas A&M University , College Station, TX 77843 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumaravel","family":"Mohankumar","sequence":"additional","affiliation":[{"name":"Department of Veterinary Physiology and Pharmacology, Texas A&M University , College Station, TX 77843 , 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