Nitric Oxide-Scavenging, Anti-Migration Effects, and Glycosylation Changes after Hemin Treatment of Human Triple-Negative Breast Cancer Cells: A Mechanistic Study.

The enhanced expression of nitric oxide (NO) synthase predicts triple-negative breast cancer outcome and its resistance to different therapeutics. Our earlier work demonstrated the efficiency of hemin to scavenge the intra- and extracellular NO, proposing its potency as a therapeutic agent for inhibiting cancer cell migration. In continuation, the present work evaluates the effects of NO on the migration of MDA-MB-231 cells and how hemin modulates the accompanied cellular behavior, focusing on the corresponding expression of cellular glycoproteins, migration-associated markers, and mitochondrial functions. We demonstrated for the first time that while NO induced cell migration, hemin contradicted that by NO-scavenging. This was in combination with modulation of the NO-enhanced glycosylation patterns of cellular proteins with inhibition of the expression of specific proteins involved in the epithelial-mesenchymal transition. These effects were in conjunction with changes in the mitochondrial functions related to both NO, hemin, and its nitrosylated product. Together, these results suggest that hemin can be employed as a potential anti-migrating agent targeting NO-scavenging and regulating the expression of migration-associated proteins.