Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
Curr Drug Targets. 2010 Dec;11(12):1551-70. doi: 10.2174/1389450111009011551.
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.
血红素加氧酶-1（HO-1）可将血红素降解为一氧化碳（CO）、胆绿素和亚铁离子。由于 HO-1 的表达会在应激条件下高度增加，因此该酶的主要作用是防止氧化损伤。此外，它还调节细胞增殖、调节炎症反应和促进血管生成。HO-1 的有益作用已在许多病理状态中得到认可，例如动脉粥样硬化、糖尿病、缺血/再灌注损伤或器官移植。有趣的是，HO-1 在肿瘤组织中的表达通常很高，并且可以对放射、化学或光动力治疗做出进一步的上调。越来越多的证据表明，HO-1 可能在肿瘤诱导中发挥作用，并能有力地促进肿瘤的生长和扩散。本文综述了 HO-1 特性对肿瘤增殖和细胞死亡、分化、血管生成和转移以及肿瘤相关炎症的影响。最后，它表明，调节 HO 活性或 HO-1 基因沉默的药理学制剂可能成为预防各种癌症发生或进展以及使它们对癌症治疗敏感的有力工具。
