Organoantimony (III) Derivative Induces Necroptosis in Human Breast Cancer MDA-MB-231 Cells

This study aimed to investigate the anticancer effect and the underlying mechanisms of organoantimony (III) fluoride on MDA-MB-231 human breast cancer cells.Five cancer and one normal cell line were treated with an organoantimony (III) compound 6-cyclohexyl-12-fluoro-5,6,7,12-tetrahydrodibenzo[c,f][1,5]azastibocine (denoted as C4). The cell viability was detected by MTT assay. Induction of cell death was determined by Hoechst 33342/PI staining and Annexin-V/PI staining. The effect of C4 on the necroptotic relative protein was determined by Western blot analysis.Among the five cancer cell lines, C4 decreased the viability of MDA-MB-231, MCF-7 and A2780/cisR, and showed less toxicity to normal human embryonic kidney cells. In breast cancer cell line MDA-MB-231, the C4 treatment induced the percentage of necrotic cell death as well as LDH releasing in a time- and dose-dependent manner. Moreover, C4 could increase the expression of phosphorylated RIPK3 and MLKL proteins. Overall, the C4 treatment resulted in reduction of mitochondrial transmembrane potential and accumulation ROS in MDA-MB-231 cells.C4-induced necroptosis could be ascribed to glutathione depletion and ROS elevation in MDA-MB-231 cells. Our findings illustrate that C4 is a potential necroptosis inducer for breast cancer treatment.