Heme oxigenase-1 has an antitumor role in breast cancer

ALONSO, E.N.; GANDINI, N.A.; FERMENTO, M.E.; MASCARÓ, M.; ABBA, M.C.; COLÓ, G.P.; ARÉVALO, J.; FERRONATO, M.J.; GUEVARA, J.A.; NUÑEZ, MYRIAM; PICHEL, PAMELA; CURINO, ALEJANDRO CARLOS; FACCHINETTI, MARÍA MARTA

ANTIOXIDANTS & REDOX SIGNALING

MARY ANN LIEBERT INC

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

1523-0864

Aims: Heme Oxygenase-1 (HO-1) is an enzyme involved in cellular responses tooxidative 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 either antitumor or protumor activity, being this also true for breast cancer (BC). In this work we intended 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 levels correlated with reduced tumor size and longer overall survival time of patients, thus suggesting the clinical importance of HO-1 in this type of cancer. Contrariwise, nuclear localization 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 both pharmacological activation and genetic overexpression of HO-1 reduce the tumor burden in two different animal models of BC. Furthermore, the pharmacological and genetic activation 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 by modulating 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 well as human tumor samples we demonstrated that total HO-1 displays antitumor activities in BC. Furthermore, our studies suggest that HO-1 subcellular localization may explain the differential effects observed for the protein in different tumor types.