A Dual Role of Heme Oxygenase-1 in Cancer Cells

• Published in: International journal of molecular sciences Vol. 20; no. 1; p. 39
• Main Authors: Chiang, Shih-Kai, Chen, Shuen-Ei, Chang, Ling-Chu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.12.2018; MDPI
• Subjects: Animals; Apoptosis; Cancer therapies; Cell Death; Cell growth; Cell Line, Tumor; Disease Models, Animal; Drug Therapy; Ferroptosis; Glutathione; Heme - metabolism; Heme Oxygenase-1 - metabolism; Humans; Iron - metabolism; Lipid Peroxidation; Neoplasms - metabolism; Oxidation; Reactive Oxygen Species - metabolism; Review; Xenograft Model Antitumor Assays; iron; ferroptosis; heme oxygenase-1; chemotherapy; glutathione; reactive oxygen species
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20010039

Heme oxygenase (HO)-1 is known to metabolize heme into biliverdin/bilirubin, carbon monoxide, and ferrous iron, and it has been suggested to demonstrate cytoprotective effects against various stress-related conditions. HO-1 is commonly regarded as a survival molecule, exerting an important role in cancer progression and its inhibition is considered beneficial in a number of cancers. However, increasing studies have shown a dark side of HO-1, in which HO-1 acts as a critical mediator in ferroptosis induction and plays a causative factor for the progression of several diseases. Ferroptosis is a newly identified iron- and lipid peroxidation-dependent cell death. The critical role of HO-1 in heme metabolism makes it an important candidate to mediate protective or detrimental effects via ferroptosis induction. This review summarizes the current understanding on the regulatory mechanisms of HO-1 in ferroptosis. The amount of cellular iron and reactive oxygen species (ROS) is the determinative momentum for the role of HO-1, in which excessive cellular iron and ROS tend to enforce HO-1 from a protective role to a perpetrator. Despite the dark side that is related to cell death, there is a prospective application of HO-1 to mediate ferroptosis for cancer therapy as a chemotherapeutic strategy against tumors.