Heme Oxygenase-1 Has an Antitumor Role in Breast Cancer

GANDINI, NORBERTO ARIEL; ALONSO, ELIANA NOELIA; FERMENTO, MARÍA EUGENIA; MASCARÓ, MARILINA; ABBA, MARTÍN CARLOS; COLÓ, GEORGINA PAMELA; ARÉVALO, JULIÁN; FERRONATO, MARÍA JULIA; GUEVARA, JOSEFINA ALEJANDRA; NÚÑEZ, MYRIAM; PICHEL, PAMELA; CURINO, ALEJANDRO CARLOS; FACCHINETTI, MARÍA MARTA

ANTIOXIDANTS & REDOX SIGNALING

MARY ANN LIEBERT INC

Año: 2019 vol. 30 p. 2030 - 2049

1523-0864

Aims: 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 cancer progression. In this regard, HO-1 has been shown to display a dual effect with either antitumor or protumor activity, which is also true for breast cancer (BC). In this work, we address this discrepancy regarding the role of HO-1 in BC. Results: HO-1 was detected in human BC 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 reduce the cellular viability by inducing apoptosis 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 Conclusion: 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 study suggests that HO-1 subcellular localization may explain the differential effects observed for the protein in different tumor types.