Valproic acid induces ferroptosis and suppresses the proliferation of MDA-MB-231 cells by targeting FDFT1

The assay outcomes indicated that VPA impedes the proliferation of breast cancer cells. The findings from the ferroptosis index demonstrated that MDA-MB-231 cells are more sensitive to VPA induced ferroptosis than MCF-7 cells. Subsequent to the introduction of ferrostatin-1 (Fer-1), Erastin or RSL3, it was observed that Fer-1 reversed the ferroptosis facilitated by VPA, whereas Erastin or RSL3, in conjunction with VPA, respectively, induced ferroptosis in MDA-MB-231 cells. We revealed that the downregulation of FDFT1 enhanced proliferation and inhibited ferroptosis of MDA-MB-231 cells. Additionally, we discovered that VPA may facilitate ferroptosis in MDA-MB-231 cells by negatively modulating the levels of the solute carrier family 7 member 11 (SLC7A11) protein through the upregulation of FDFT1 expression. In conclusion, this study elucidated that VPA induced the ferroptosis of MDA-MB-231 cells via targeting FDFT1, representing a novel mechanism underlying its efficacy in potentially inhibiting breast cancer.