Heme oxygenase-1: emerging target of cancer therapy

Heme oxygenase-1 (HO-1) is a rate-limiting enzyme catalyzing oxidative degradation of cellular heme to liberate free iron, carbon monoxide (CO) and biliverdin in mammalian cells. In addition to its primary role in heme catabolism, HO-1 exhibits anti-oxidative and anti-inflammatory functions via the actions of biliverdin and CO, respectively. HO-1 is highly induced in various disease states, including cancer. Several lines of evidence have supported the implication of HO-1 in carcinogenesis and tumor progression. HO-1 deficiency in normal cells enhances DNA damage and carcinogenesis. Nevertheless, HO-1 overexpression in cancer cells promotes proliferation and survival. Moreover, HO-1 induces angiogenesis through modulating expression of angiogenic factors. Although HO-1 is an endoplasmic reticulum resident protein, HO-1 nuclear localization is evident in tumor cells of cancer tissues. It has been shown that HO-1 is susceptible to proteolytic cleavage and translocates to nucleus to facilitate tumor growth and invasion independent of its enzymatic activity. HO-1 also impacts cancer progression through modulating tumor microenvironment. This review summarizes the current understanding of the protumorigenic role of HO-1 and its potential as a molecular target for cancer therapy.