Quercetin inhibits breast cancer progression by inducing ferroptosis via the NEDD4L-SLC7A11 axis.

Breast cancer remains one of the most serious malignancies threatening women's health. Quercetin, a major active component found in various Chinese herbal medicines, has shown antitumor potential; however, its specific role and underlying mechanisms in breast cancer require systematic investigation. This study demonstrated through MTT, colony formation, wound healing, and Transwell assays that quercetin significantly inhibits the viability, proliferation, and migration capabilities of breast cancer cells. Transcriptome sequencing combined with biochemical assays, qPCR, and Western blot further indicated that quercetin can induce ferroptosis, which is likely the key mechanism underlying its suppression of malignant progression in breast cancer cells. Mechanistically, by promoting the binding between the E3 ubiquitin ligase NEDD4L and SLC7A11, quercetin induces the ubiquitin-proteasome degradation of SLC7A11, ultimately leading to ferroptosis. Notably, quercetin maintained a significant inhibitory effect even during the malignant transformation of breast cancer cells induced by heavy metal lead (Pb) exposure. Collectively, these findings suggest a potential mechanism by which quercetin may inhibits breast cancer progression through ferroptosis activation via the NEDD4L/SLC7A11 axis, offering preliminary evidence that could support its possible therapeutic application in breast cancer.