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Silibinin inhibits expression of HIF-1α through suppression of protein translation in prostate cancer cells

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Author(s)
박종욱이성용장병철서성일서민호백원기
Alternative Author(s)
Park, Jong WookLee, Seong RyongJang, Byeong ChurlSuh, Seong IlSuh, Min HoBaek, Won Ki
Publication Year
2009
Abstract
Silibinin is a polyphenolic flavonoid isolated from the milk thistle (Silybum marianum) and is reported to exhibit anticancer properties. Recently, it has been reported that silibinin inhibits hypoxia-inducible factor-1α (HIF-1α) expression in cancer cells. However, the precise mechanism by which silibinin decreases HIF-1 expression is not fully understood. In this study, silibinin inhibited basal and hypoxia induced expression levels of HIF-1α protein in LNCaP and PC-3 prostate cancer cells, while the rate of HIF-1α protein degradation and mRNA levels were not affected. We found that the decrease in HIF-1 protein by silibinin correlated with suppression of de novo synthesis of HIF-1α protein. Silibinin inhibited global protein synthesis coincided with reduction of eIF4F complex formation and induction of phosphorylation of the translation initiation factor 2α (eIF-2α) which can cause inhibition of general protein synthesis. These results suggest that silibinin’s activity to inhibit HIF-1α protein expression is associated with the suppression of global protein translation.

Keywords
Hypoxia-inducible factor-1α;
Silibinin;
Protein translation;
Prostate cancer
Department
Dept. of Immunology (면역학)
Dept. of Pharmacology (약리학)
Dept. of Molecular Medicine (분자의학)
Dept. of Microbiology (미생물학)
Publisher
School of Medicine
Citation
Biochemical and Biophysical Research Communications, Vol.390(1) : 71-76, 2009
Type
Article
ISSN
0006-291X
DOI
10.1016/j.bbrc.2009.09.068
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35202
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