New anticancer strategies targeting HIF-1

• Published in: Biochemical pharmacology 2004-09, Vol.68 (6), p.1061-1069
• Main Authors: Yeo, Eun-Jin, Chun, Yang-Sook, Park, Jong-Wan
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological - physiology; Angiogenesis; Animals; Anticancer chemotherapy; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Cancer; Cell Transformation, Neoplastic; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Gene Targeting; HIF; Humans; Hypoxia; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Indazoles - pharmacology; Medical sciences; Neoplasms - drug therapy; Neoplasms - therapy; Nuclear Proteins - antagonists & inhibitors; Nuclear Proteins - genetics; Nuclear Proteins - physiology; Pharmacology. Drug treatments; Transcription Factors; YC-1
• ISSN: 0006-2952; 1873-2968
• 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.