|
KMID : 0811720100140050331
|
|
Korean Journal of Physiology & Pharmacology
2010 Volume.14 No. 5 p.331 ~ p.336
|
|
|
CaMKII Inhibitor KN-62 Blunts Tumor Response to Hypoxia by Inhibiting HIF-1? in Hepatoma Cells
|
|
Lee Kyoung-Hwa
|
|
|
Abstract
|
|
|
|
In rapidly growing tumors, hypoxia commonly develops due to the imbalance between O2 consumption and supply. Hypoxia Inducible Factor (HIF)-1? is a transcription factor responsible for tumor growth and angiogenesis in the hypoxic microenvironment; thus, its inhibition is regarded as a promising strategy for cancer therapy. Given that CamKII or PARP inhibitors are emerging anticancer agents, we investigated if they have the potential to be developed as new HIF-1?-targeting drugs. When treating various cancer cells with the inhibitors, we found that a CamKII inhibitor, KN-62, effectively suppressed HIF-1? specifically in hepatoma cells. To examine the effect of KN-62 on HIF-1?- driven gene expression, we analyzed the EPO-enhancer reporter activity and mRNA levels of HIF-1? downstream genes, such as EPO, LOX and CA9. Both the reporter activity and the mRNA expression were repressed by KN-62. We also found that KN-62 suppressed HIF-1? by impairing synthesis of HIF-1? protein. Based on these results, we propose that KN-62 is a candidate as a HIF-1?-targeting anticancer agent.
|
|
|
KEYWORD
|
|
|
CaMKII, HIF1-?, Hepatocellular carcinoma, Hypoxia, KN-62
|
|
|
FullTexts / Linksout information
|
|
 
|
|
|
Listed journal information
|
|
  
|
|