Heme oxygenase-1 is involved in the erastin-induced ferroptosis in acute myeloid leukemia cells

Abstract Emerging evidences have suggested that ferroptosis is one of the targeted mechanisms in tumor therapy. However, whether erastin can induce ferroptosis in acute myeloid leukemia (AML) and the potential mechanisms remains to be explored. CCK8 assay was first used to detect the toxicity of erastin to human promyelocytic leukemia cells (HL60), and the toxicological effect of erastin on HL60 cells performed a significant dose-dependent manner. Ferroptosis in HL60 was affirmed through the manifestation of mitochondrial ultrastructural damage, accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), depletion of glutathione (GSH) and glutathione peroxidase (GPX)4. Proteomics analysis identified heme oxygenase-1 (HO-1) as a key protein involved in the ferroptosis pathway. Further experiments showed that activation of HO-1 with Hemin worsened erastin-induced ferroptosis, while inhibition of HO-1 with Znpp partially alleviated it , without affecting protein levels of P62, LC3B, and nuclear receptor coactivator (NCOA)4. Thus, our study has indicated that erastin significantly induced ferroptosis in HL60 cells, which can be reversed by ferrostatin-1 (Fer-1). Overexpression of HO-1 deteriorates erastin-induced ferroptosis, which can be partially alleviated by inhibition of HO-1 independent on ferritinophagy. Ferroptosis, as a new cell death mechanism, may provide new clues and strategies for the treatment of AML.