HO-1/CO system in tumor growth, angiogenesis and metabolism — Targeting HO-1 as an anti-tumor therapy

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• 作者：Agnieszka Loboda^a ; ^b ; ^{agnieszka.loboda@uj.edu.pl" class="auth_mail" title="E-mail the corresponding author} ; Alicja Jozkowicz^a ; Jozef Dulak^a ; ^b ; ^{jozef.dulak@uj.edu.pl" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ALLs ; acute lymphoblastic leukemia cells ; BVR ; biliverdin reductase ; CML ; chronic myelogenous leukemia ; CO ; carbon monoxide ; CORM ; carbon monoxide-releasing molecule ; CrMP ; chromium mesoporphyrin ; CrPP ; chromium protoporphyrin ; HO-1 ; heme oxygenase-1 ; HRPCA ; hormone refractory prostate cancer ; IDO ; indoleamine 2 ; 3-dioxygenase ; NSCLC ; non-small-cell lung carcinoma ; RMS ; rhabdomyosarcoma ; ROS ; reactive oxygen species ; SDF-1 ; stromal cell-derived factor-1 ; SnPP ; tin protoporphyrin ; ZnDP ; zinc deute
• 刊名：Vascular Pharmacology
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：74
• 期：Complete
• 页码：11-22
• 全文大小：855 K

文摘

Heme oxygenase-1 (HO-1, hmox-1) catalyzes the rate-limiting step in the heme degradation processes. Out of three by-products of HO-1 activity, biliverdin, iron ions and carbon monoxide (CO), the latter was mostly shown to mediate many beneficial HO-1 effects, including protection against oxidative injury, regulation of apoptosis, modulation of inflammation as well as contribution to angiogenesis. Mounting evidence suggests that HO-1/CO system may be of special benefit in protection in many pathological conditions, like atherosclerosis or myocardial infarction. By contrast, the augmented expression of HO-1 in tumor tissues may have detrimental effect as HO-1 accelerates the formation of tumor neovasculature and provides the selective advantage for tumor cells to overcome the increased oxidative stress during tumorigenesis and during treatment. The inhibition of HO-1 has been proposed as an anti-cancer therapy, however, because of non-specific effects of known HO-1 inhibitors, the discovery of ideal drug lowering HO-1 expression/activity is still an open question. Importantly, in several types of cancer HO-1/CO system exerts opposite activities, making the possible treatment more complicated. All together indicates the complex role for HO-1/CO in various in vitro and in vivo conditions.