Heme Oxygenase-1 Impairs Hormone-Dependent Breast Cancer Cell Survival Through its Enzyme Activity

GIORGI, G.; SCHWEITZER, K.; MASCARÓ, M.; RABASSA, MARTÍN E.; FLORENCIA, M.; COLÓ, G.P.; FERMENTO, M.E.; FERRONATO, M.J.; ALONSO, E.N.; CURINO, A.C.; FACCHINETTI, M.M.

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencia; 2023

We have previously reported that induction of Heme Oxygenase-1 (HO-1), an enzyme that catalyzes heme degradation and releases iron, impairs breast cancer (BC) cell survival in both murine hormone-independent (LM3) and human triple-negative (MDA-MB-231) BC cell lines, most likely through ferroptosis induction. In this study, we aimed to evaluate the HO-1 modulation on hormone-dependent BC cell survival and to assess the involvement of HO-1 enzyme activity. To this end, we modulated HO-1 in T47D cell line by pharmacological induction (hemin, 36h) and by stable overexpression of wild-type HO1 (WT-HO1) or enzymatically inactive-H25AHO-1 (H25A). We studied cell viability (crystal violet), iron storage (Prussian blue), ROS levels (DFCA), lipid peroxidation (MDA accumulation) and the expression of ZIP14 iron importer (immunocytochemistry). We also carried out correlation studies between HO-1 mRNA levels and L-ferritin in BC subtypes (bioinformatics analysis). We found that hemin treatment and WT-HO1 overexpression decreased T47D cell viability (p