SBFI26 induces triple-negative breast cancer cells ferroptosis via lipid peroxidation.

1. J Cell Mol Med. 2024 Apr;28(7):e18212. doi: 10.1111/jcmm.18212. SBFI26 induces triple-negative breast cancer cells ferroptosis via lipid peroxidation. He G(1), Zhang Y(1), Feng Y(1), Chen T(1), Liu M(1), Zeng Y(1), Yin X(1), Qu S(1), Huang L(1), Ke Y(1), Liang L(1), Yan J(1), Liu W(1). Author information: (1)Key Laboratory of Medicinal and Edible Plants Resources Development of Sichuan Education Department, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, China. SBFI26, an inhibitor of FABP5, has been shown to suppress the proliferation and metastasis of tumour cells. However, the underlying mechanism by which SBFI26 induces ferroptosis in breast cancer cells remains largely unknown. Three breast cancer cell lines were treated with SBFI26 and CCK-8 assessed cytotoxicity. Transcriptome was performed on the Illumina platform and verified by qPCR. Western blot evaluated protein levels. Malondialdehyde (MDA), total superoxide dismutase (T-SOD), Fe, glutathione (GSH) and oxidized glutathione (GSSG) were measured. SBFI26 induced cell death time- and dose-dependent, with a more significant inhibitory effect on MDA-MB-231 cells. Fer-1, GSH and Vitamin C attenuated the effects but not erastin. RNA-Seq analysis revealed that SBFI26 treatment significantly enriched differentially expressed genes related to ferroptosis. Furthermore, SBFI26 increased intracellular MDA, iron ion, and GSSG levels while decreasing T-SOD, total glutathione (T-GSH), and GSH levels.SBFI26 dose-dependently up-regulates the expression of HMOX1 and ALOX12 at both gene and protein levels, promoting ferroptosis. Similarly, it significantly increases the expression of SAT1, ALOX5, ALOX15, ALOXE3 and CHAC1 that, promoting ferroptosis while downregulating the NFE2L2 gene and protein that inhibit ferroptosis. SBFI26 leads to cellular accumulation of fatty acids, which triggers excess ferrous ions and subsequent lipid peroxidation for inducing ferroptosis. © 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. DOI: 10.1111/jcmm.18212 PMCID: PMC10958404 PMID: 38516826 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no conflicts of interest.