Etoposide in combination with erastin synergistically altered iron homeostasis and induced ferroptotic cell death through regulating IREB2/FPN1 expression in estrogen receptor positive-breast cancer cells

Ferroptosis is an iron-dependent cell death mechanism that substantially differs from apoptosis. Since its mechanism involves increased oxidative stress and rich iron content, cancer cells are particularly vulnerable to ferroptotic death compared to healthy tissues. In the present study, the effect of etoposide in combination with a ferroptotic agent, erastin, was investigated in breast cancer. Cell viability was assessed by the MTT assay. Oxidative stress, lipid peroxidation and glutathione peroxidase activity were detected using the relevant kits. Intracellular iron levels were measured by HPLC. Ferroptosis markers were explored by western blotting. Results demonstrated that although etoposide didn't induce a significant cell death up to 50 μM in MCF-7 cells, with the addition of erastin, a significant synergistic activity was achieved at a dose as low as 1 μM (p