Heme Oxygenase-1 Has an Antitumor Role in Breast Cancer

GANDINI, N.A.; MASCARÓ, M.; ARÉVALO, J.; NÚÑEZ, M.; FACCHINETTI, M.M.; ALONSO, E.N.; ABBA, M.C.; FERRONATO, M.J.; PICHEL, P.; FERMENTO, M.E.; COLÓ, G. P.; GUEVARA, J.A.; CURINO, A.C.

ANTIOXIDANTS & REDOX SIGNALING

MARY ANN LIEBERT INC

Lugar: New York; Año: 2019 vol. 30 p. 2030 - 2049

1523-0864

Heme Oxygenase-1 (HO-1) is an enzyme involved in cellular responses to oxidative stress and has also been shown to regulate processes related to cancerprogression. In this regard, HO-1 has been shown to display a dual effect with eitherantitumor or protumor activity, being this also true for breast cancer (BC). In this work weintended to address this discrepancy regarding the role of HO-1 in BC.Results: HO-1 was detected in human breast cancer tissues, and its protein levelscorrelated with reduced tumor size and longer overall survival time of patients, thussuggesting the clinical importance of HO-1 in this type of cancer. Contrariwise, nuclearlocalization of HO-1 correlated with higher tumor grade suggesting that the effect of HO-1 is dependent on its cellular localization. In vivo experiments showed that bothpharmacological activation and genetic overexpression of HO-1 reduce the tumor burdenin two different animal models of BC. Furthermore, the pharmacological and geneticactivation of HO-1 in several BC cell lines both reduce the cellular viability by inducingapoptosis and cell cycle arrest and decrease the cellular migration and invasion rates bymodulating pathways involved in the epithelial-mesenchymal transition. Furthermore,HO-1 activation impaired in vivo the metastatic dissemination.Innovation and conclusions: by using various BC cell lines and animal models as wellas human tumor samples we demonstrated that total HO-1 displays antitumor activitiesin BC. Furthermore, our studies suggest that HO-1 subcellular localization may explainthe differential effects observed for the protein in different tumor types.