INHIBITION OF HO-1 ENZYMATIC ACTIVITY IMPAIRS HEAD AND NECK CANCER CELL SURVIVAL

MASCARÓ, M.; ALONSO, E.G.; SCHWEITZER, K.; FERNÁNDEZ CHÁVEZ, L.; FERRONATO, M.J.; IBARRA, A.; COLÓ, G.P.; GIORGI, G.; CURINO, A.C.; FACCHINETTI, M.M.

Congreso; Reunión Anual de Sociedades de Biociencia; 2021

Sociedad Argentina de Investigaciones Clínicas

We have previously reported that, in human HNSCC samples, hemeoxygenase-1 (HO-1) mRNA expression is up-regulated and it is associated with worst survival. We also reported an up-regulation of HO-1 protein levels and that it is localized in the cytoplasmic and nuclear compartments. Moreover, we demonstrated that pharmacological activation of HO-1 by hemin and genetic full-length HO-1 (FL-HO-1) overexpression increases HN13 cells survival and cell cycle progression, suggesting a protumor role of HO-1 in HNSCC. However, whether byproducts of HO-1 enzymatic activity are involved in FL-HO-1 mediated-effects remains unknown. In this study, we aimed to elucidate if inhibition of HO-1 enzymatic activity impacts on head and neck cancer cells behavior. To that end, HO-1 activity was inhibited pharmacologically using ZnPP and an enzymatically inactive FL-H25A-HO1-overexpressing HN13 cell line was established. We evaluated HO-1 expression by western blot and indirect immunofluorescence, cell viability by crystal violet, cell proliferation by manual cell counting, cell cycle progression by propidium iodide staining and flow cytometry, and cell migration by wound healing assay. We found that 10 µM ZnPP impaired cell viability (p