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

Authors
Hui-Jung JungIncheol SeoBijay Kumar JhaSeong-Il SuhMin-Ho SuhWon-Ki Baek
Department
Dept. of Microbiology (미생물학)
Issue Date
2014
Citation
Archives of Biochemistry and Biophysics, Vol.545() : 74-82, 2014
ISSN
0003-9861
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
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35083
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
Keimyung Author(s)
서성일; 서민호; 백원기
Full Text
https://linkinghub.elsevier.com/retrieve/pii/S0003986114000022
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