Yeo Eun-Jin, Chun Yang-Sook, Park Jong-Wan
Department of Pharmacology, College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, 110-799, Republic of Korea.
Biochem Pharmacol. 2004 Sep 15;68(6):1061-9. doi: 10.1016/j.bcp.2004.02.040.
Hypoxia-inducible factor-1 (HIF-1), which is present at high levels in human tumors, plays crucial roles in tumor promotion by up-regulating its target genes, which are involved in anaerobic energy metabolism, angiogenesis, cell survival, cell invasion, and drug resistance. Therefore, it is apparent that the inhibition of HIF-1 activity may be a strategy for treating cancer. Recently, many efforts to develop new HIF-1-targeting agents have been made by both academic and pharmaceutical industry laboratories. The future success of these efforts will be a new class of HIF-1-targeting anticancer agents, which would improve the prognoses of many cancer patients. This review focuses on the potential of HIF-1 as a target molecule for anticancer therapy, and on possible strategies to inhibit HIF-1 activity. In addition, we introduce YC-1 as a new anti-HIF-1, anticancer agent. Although YC-1 was originally developed as a potential therapeutic agent for thrombosis and hypertension, recent studies demonstrated that YC-1 suppressed HIF-1 activity and vascular endothelial growth factor expression in cancer cells. Moreover, it halted tumor growth in immunodeficient mice without serious toxicity during the treatment period. Thus, we propose that YC-1 is a good lead compound for the development of new anti-HIF-1, anticancer agents.
缺氧诱导因子-1（HIF-1）在人类肿瘤中高水平存在，通过上调其靶基因在肿瘤进展中发挥关键作用，这些靶基因参与无氧能量代谢、血管生成、细胞存活、细胞侵袭和耐药性。因此，抑制HIF-1活性显然可能是一种治疗癌症的策略。最近，学术和制药行业实验室都在努力开发新的HIF-1靶向剂。这些努力未来的成功将是一类新的HIF-1靶向抗癌剂，这将改善许多癌症患者的预后。本综述重点关注HIF-1作为抗癌治疗靶分子的潜力，以及抑制HIF-1活性的可能策略。此外，我们介绍了YC-1作为一种新的抗HIF-1抗癌剂。尽管YC-1最初是作为一种潜在的血栓形成和高血压治疗剂开发的，但最近的研究表明，YC-1可抑制癌细胞中的HIF-1活性和血管内皮生长因子表达。此外，它在免疫缺陷小鼠中可使肿瘤生长停止，且在治疗期间无严重毒性。因此，我们认为YC-1是开发新型抗HIF-1抗癌剂的良好先导化合物。
