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)-N-center dot) 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)-N-center dot, proposing its potency as a therapeutic agent for inhibiting cancer cell migration. In continuation, the present work evaluates the effects of (NO)-N-center dot on the migration of MDA-MB-231 cells and how hemin modulates the accompanied cellular behavior, focusing on the corresponding expression of cellular glycoproteins, migrationassociated markers, and mitochondrial functions. We demonstrated for the first time that while (NO)-N-center dot induced cell migration, hemin contradicted that by (NO)-N-center dot-scavenging. This was in combination with modulation of the (NO)-N-center dot-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)-N-center dot, hemin, and its nitrosylated product. Together, these results suggest that hemin can be employed as a potential antimigrating agent targeting (NO)-N-center dot-scavenging and regulating the expression of migration-associated proteins.

Automated summary

The study demonstrates that hemin can be used as a potential anticancer agent by scavenging nitric oxide (NO), inhibiting cancer cell migration, and regulating the expression of migration-associated proteins.