Phillyrin restrains breast cancer cell growth by inducing ferroptosis

Background: Breast cancer is one of the most common malignant tumors worldwide, predominantly affecting women and associated with high mortality. Phillyrin (PHN), a bioactive compound isolated from Forsythia suspensa (Thunb.) Vahl has been confirmed to possess diverse biological activities, including anti-inflammatory, antioxidant, and anti-tumor effects. Nevertheless, its regulatory role in breast cancer progression remains unclear. Methods: Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay, while proliferative capacity was evaluated through colony formation assay. Apoptosis was determined by flow cytometry. The level of reactive oxygen species (ROS) was measured by 2′,7′-dichlorofluorescein diacetate (DCFH-DA) staining. The concentrations of malondialdehyde (MDA), glutathione (GSH), and Fe2+ were quantified using the corresponding detection kits. Protein expression levels were analyzed by western blotting. Results: PHN significantly inhibited breast cancer cell growth and induced ferroptosis. Treatment with 50 µmol/L PHN reduced cell proliferation, an effect that was reversed by Ferrostatin-1 (Fer-1), a ferroptosis inhibitor. Furthermore, PHN was shown to suppress activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Conclusions: PHN inhibited breast cancer cell growth by inducing ferroptosis and suppressing the PI3K/Akt pathway. These findings suggest that PHN may represent a potential therapeutic agent for the treatment of breast cancer.

Phillyrin; Ferroptosis; PI3K/Akt pathway; Breast cancer

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