Effects of different therapeutic agents on ferroptosis in endometriotic and human breast cancer cell lines

Ferroptosis is a form of regulated cell death driven by intracellular iron accumulation and lipid peroxidation, based on oxidative stress. This mechanism plays distinct roles in inflammatory diseases and malignancies. In this study, the effects of EGCG, Curcumin, Chrysin, and Quercetin on ferroptosis-related genes were investigated in HEC1A (endometrial adenocarcinoma) and MCF-7/S0.5 (breast cancer) cell lines. The expression levels of GPX4, SLC7A11, NRF2, CASP3, VEGFC, and FBLN1 genes were analyzed using qPCR, while GPX4, SLC7A11, and 4-HNE protein levels were evaluated by Western blot analysis. At 48 hours, EGCG treatment significantly increased the expression of VEGFC and FBLN1; however, these changes varied depending on cell line and treatment conditions. In HEC1A cells, Curcumin and Chrysin suppressed GPX4 and SLC7A11 levels while enhancing lipid peroxidation, which was associated with strong ferroptotic responses. In the MCF-7/S0.5 line, Curcumin decreased the expression of GPX4 and FBLN1, while increasing SLC7A11. Quercetin showed limited effects in both models. Discrepancies between gene and protein expression levels suggested a potential role of post-translational regulatory mechanisms. Overall, the results demonstrated that natural polyphenols can bidirectionally modulate the ferroptosis pathway in a cell type- and context-dependent manner, and elicit specific molecular responses in certain markers. Although the HEC1A cell line does not directly represent benign endometriosis, it was included as an endometrial-origin model in this context. The findings suggest that these compounds may serve as promising therapeutic agents in ferroptosis-based targeted treatment strategies.