계명대학교 의학도서관 Repository

Translational suppression of HIF-1α by miconazole through the mTOR signaling pathway

Metadata Downloads
Author(s)
Jee-Young ParkHui-Jung JungIncheol SeoBijay Kumar JhaSeong-Il SuhMin-Ho SuhWon-Ki Baek
Keimyung Author(s)
Suh, Seong IlSuh, Min HoBaek, Won Ki
Department
Dept. of Microbiology (미생물학)
Journal Title
Cellular Oncology
Issued Date
2014
Volume
37
Issue
4
Abstract
Background : Miconazole is an imidazole antifungal agent that has amply been used in the treatment of superficial mycosis. Preliminary data indicate that miconazole may also induce anticancer effects. As yet, however, little is known about the therapeutic efficacy of miconazole on cancer and the putative mechanism(s) involved. Here, we show that miconazole suppresses hypoxia inducible factor-1α (HIF-1α) protein translation in different cancer-derived cells.

Methods : The effect of miconazole on HIF-1α expression was examined by Western blotting and reverse transcriptase polymerase chain reaction assays in human U87MG and MCF-7 glioma and breast cancer-derived cell lines, respectively. The transcriptional activity of the HIF-1 complex was confirmed using a luciferase assay. To assess whether angiogenic factors are increased under hypoxic conditions in these cells, vascular endothelial growth factor (VEGF) levels were measured by ELISA. Metabolic labeling was performed to examine HIF-1α protein translation and global protein synthesis. The role of the mammalian target of rapamycin (mTOR) signaling pathway was examined to determine translation regulation of HIF-1α after miconazole treatment.

Results : Miconazole was found to suppress HIF-1α protein expression through post-transcriptional regulation in U87MG and MCF-7 cells. The suppressive effect of HIF-1α protein synthesis was found to be due to inhibition of mTOR. Miconazole significantly inhibited the transcriptional activity of the HIF-1 complex and the expression of its target VEGF. Moreover, miconazole was found to suppress global protein synthesis by inducing phosphorylation of the translation initiation factor 2α (eIF2α).

Conclusion : Our data indicate that miconazole plays a role in translational suppression of HIF-1α. We suggest that miconazole may represent a novel therapeutic option for the treatment of cancer.

Keywords : HIF-1 – VEGF – Miconazole – mTOR – eIF2α
Keimyung Author(s)(Kor)
서성일
서민호
백원기
Publisher
School of Medicine
Citation
Jee-Young Park et al. (2014). Translational suppression of HIF-1α by miconazole through the mTOR signaling pathway. Cellular Oncology, 37(4), 269–279. doi: 10.1007/s13402-014-0182-8
Type
Article
ISSN
2211-3428
Source
https://link.springer.com/article/10.1007%2Fs13402-014-0182-8
DOI
10.1007/s13402-014-0182-8
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35381
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
공개 및 라이선스
  • 공개 구분공개
  • 엠바고Forever
파일 목록

Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.