Regulating Effect of Cytochrome b5 Overexpression on Human Breast Cancer Cells

Imbalance in the cellular redox system is thought to be associated with the induction and progression of breast cancers, and heme proteins may regulate the redox balance. Cytochromeb5(Cytb5) is a small mitochondrial heme protein. Its function and regulating mechanism in breast cancer remain unknown. In this study, we elucidated the level of endogenous oxidative stress in breast cancer cells, MCF-7 cells (hormone receptor-positive cells) and MDA-MB-231 cells (triple-negative cells), and investigated the difference in Cytb5content. Based on the low content of Cytb5in MDA-MB-231 cells, the overexpression of Cytb5was found to regulate the oxidative stress and apoptosis cascades, including ERK1/2 and Akt signaling pathways. The overexpressed Cytb5MDA-MB-231 cells were shown to exhibit decreased oxidative stress, less phosphorylation of ERK1/2 and Akt, and less cleavage of caspases 3 and 9 upon treatment with H2O2, as compared to those of normal MDA-MB-231 cells. Moreover, the overexpressed Cytb5most likely functioned by interacting with its protein partner, Cytc, as suggested by co-immunoprecipitation studies. These results indicated that Cytb5has different effects on breast cancer cells of different phenotypes, which provides useful information for understanding the multiple roles of Cytb5and provides clues for clinical treatment.Keywords:Cytochromeb5;Cytochromec;protein-protein interactions;breast cancer cells;co-immunoprecipitation