The Paradox of Heme Oxygenase 1: From Cellular Defense to a Tug of War between Cancer Promotion and Prevention

The Hmox1 enzyme, which is the inducible enzyme among the Hmoxs, catalyzes the first and rate-limiting step in the heme degradation pathway, generating three byproducts, namely, carbon monoxide, free iron, and biliverdin. These byproducts can affect an array of biological processes; hence, Hmox1 modulates multiple metabolic processes. Along with the degradation of cytotoxic heme, Hmox1 provides protection against inflammation, apoptosis, and oxidative stress. It also ameliorates tissue injury, maintains iron homeostasis, and supports embryonic survival. Initially, different studies labeled it as an active cancer-assisting agent; however, multiple recent studies have shown that it also deters cancer progression. Hence, this review first looks into the traditional role of Hmox1 and various Hmox1 inducers. Second, there are multiple links between Hmox1 and different types of cancer, including how it acts as a promoter or plays an antitumor role in different or even the same cancers. On the basis of the available data, the work proposes a few speculations to explain this dual role of Hmox1 in cancer.