New anticancer strategies targeting HIF-1.
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.
Yeo
Eun-Jin
EJ
Department of Pharmacology, College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, 110-799, Republic of Korea.
Chun
Yang-Sook
YS
Park
Jong-Wan
JW
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D018390:Gene Targeting; D006801:Humans; D000860:Hypoxia; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007191:Indazoles / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy / Q000628:therapy; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007191:Indazoles; D009687:Nuclear Proteins; D014157:Transcription Factors; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole