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Minocycline inhibits angiogenesis in vitro through the translational suppression of HIF-1α

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Author(s)
서성일서민호백원기
Alternative Author(s)
Suh, Seong IlSuh, Min HoBaek, Won Ki
Publication Year
2014
Abstract
Minocycline was recently found to be effective against cancer. However, the precise molecular mechanisms of minocycline in cancer are poorly understood. Hypoxia-inducible factor-1 (HIF-1, a heterodimeric transcription factor composed of HIF-1α and β) activates the transcription of genes that are involved in angiogenesis in cancer. In this study, we found that minocycline significantly inhibits HIF-1α protein expression and suppresses HIF-1 transcriptional activity. The tube formation assay showed that minocycline has anti-angiogenic activity and suppresses hypoxia-induced vascular endothelial growth factor (VEGF) expression. The metabolic labeling assay showed that minocycline reduces HIF-1α protein translation and global protein synthesis. In addition, minocycline suppresses mTOR signaling and increases the phosphorylation of eIF2α, which is known to be related to the translational regulation of HIF-1α expression. These findings collectively indicate that minocycline is a potential inhibitor of HIF-1α and provide new insight into the discovery of drugs for cancer treatment.

Keywords
HIF-1;
VEGF;
Minocycline;
mTOR
Department
Dept. of Microbiology (미생물학)
Publisher
School of Medicine
Citation
Archives of Biochemistry and Biophysics, Vol.545(null) : 74-82, 2014
Type
Article
ISSN
0003-9861
DOI
10.1016/j.abb.2013.12.023
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35083
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