Heme oxygenase-1 in tumor biology and therapy.
Heme oxygenase-1 (HO-1) degrades heme to carbon monoxide (CO), biliverdin, and ferrous iron. As HO-1 expression is highly increased by stressful conditions, the major role of the enzyme is the protection against oxidative injury. Additionally, it regulates cell proliferation, modulates inflammatory response and facilitates angiogenesis. Beneficial activities of HO-1 have been recognized in many pathological states e.g. atherosclerosis, diabetes, ischemia/reperfusion injury or organ transplantation. Interestingly HO-1 expression is very often boosted in tumor tissues and could be further elevated in response to radio-, chemo-, or photodynamic therapy. A growing body of evidence suggests that HO-1 may play a role in tumor induction and can potently improve the growth and spread of tumors. This review discusses the implications of HO-1 properties for tumor proliferation and cell death, differentiation, angiogenesis and metastasis, and tumor-related inflammation. Finally, it suggests that pharmacological agents that regulate HO activity or HO-1 gene silencing may become powerful tools for preventing the onset or progression of various cancers and sensitize them to anticancer therapies.
Was
Halina
H
Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
Dulak
Jozef
J
Jozkowicz
Alicja
A
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000503:physiopathology / Q000517:prevention & control; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects; D011110:Polymorphism, Genetic; D011230:Precancerous Conditions / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control
D000894:Anti-Inflammatory Agents, Non-Steroidal; D051547:Heme Oxygenase-1