Heme Oxygenase-1 Has an Antitumor Role in Breast Cancer

Abstract

Aims:Heme oxygenase-1 (HO-1) is an enzyme involved in cellular responses to oxidative stress and has alsobeen shown to regulate processes related to cancer progression. In this regard, HO-1 has been shown to displaya 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 longeroverall 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 tumorgrade suggesting that the effect of HO-1 is dependent on itscellular localization.In vivoexperiments showed that both pharmacological activation and genetic overexpression ofHO-1 reduce the tumor burden in two different animal models of BC. Furthermore, the pharmacological and geneticactivation of HO-1 in several BC cell lines reduce the cellular viability by inducing apoptosis and cell cycle arrest anddecrease the cellular migration and invasion rates by modulating pathways involved in the epithelial–mesenchymaltransition. Furthermore, HO-1 activation impairedin vivothe metastatic dissemination.Innovation and Conclusion:By using various BC cell lines and animal models as well as human tumorsamples, we demonstrated that total HO-1 displays antitumor activities in BC. Furthermore, our study suggeststhat HO-1 subcellular localization may explain the differential effects observed for the protein in differenttumor types.