Hypoxia is generally detected in central regions of solid tumors and regulates a variety of transcription factors including hypoxia-inducible factor-1 (HIF-1). HIF-1 plays a pivotal role in cellular response to low oxygen concentration, such as angiogenesis in tumor. Here, we found that a histone deacetylase (HDAC) inhibitor, FK228, inhibits the induction and activity of HIF-1 in response to hypoxia. Moreover, FK228 significantly suppressed the induction of vascular endothelial growth factor (VEGF) under hypoxia, suggesting that FK228 contributes to the inhibition of tumor angiogenesis. In Lewis lung carcinoma model, FK228 also blocked angiogenesis induced by hypoxia. These results suggest that FK228 can downregulate hypoxia-responsive angiogenesis through suppression of HIF-1α activity.
|Number of pages||6|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2003|
Bibliographical noteFunding Information:
This work was supported by a grant from the Korea Health 21 R&D Project (HMP-01-PJ1-PG1-01CH04-0005), Ministry of Health and Welfare, Korea.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology