Darolutamide-mediated phospholipid remodeling induces ferroptosis through the SREBP1-FASN axis in prostate cancer.

ABSTRACT: Darolutamide, an androgen receptor inhibitor, has been approved by the Food and Drug Administration (FDA) for the treatment of prostate cancer (PCa), especially for patients with androgen receptor mutations. Owing to the unique lipidomic profile of PCa and the effect of darolutamide, the relationship between darolutamide and ferroptosis remains unclear. The present study showed that darolutamide significantly induces ferroptosis in AR⁺ PCa cells. Mechanistically, darolutamide promotes ferroptosis by downregulating SREBP1, which then inhibits the transcription of FASN. FASN knockdown modulates phospholipid remodeling by disrupting the balance between polyunsaturated fatty acids (PUFAs) and saturated fatty acids (SFAs), which induces ferroptosis. Clinically, SREBP1 and FASN are si

SUBMITTER: Li B 

PROVIDER: S-EPMC11414384 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature