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|Title: ||Cholestane-3β, 5α, 6β-triol Suppresses Proliferation, Migration, and Invasion of Human Prostate Cancer Cells|
|Authors: ||Ching-Yu Lin;Chieh Huo;Li-Kuo Kuo;Richard A. Hiipakka;Richard Baker Jones;Hui-Ping Lin;Yuwen Hung;Liang-Cheng Su;Jen-Chih Tseng;Ying-Yu Kuo;Yu-Ling Wang;Yasuhisa Fukui;Yung-Hsi Kao;John M. Kokontis;Chien-Chih Yeh;Linyi Chen;Shiaw-Der Yang;Hsiao-Hui Fu;Ya-Wen Chen;Kelvin K.-C. Tsai;Jang-Yang Chang;Chih-Pin Chuu|
|Publisher: ||Public Library of Science|
|Relation: ||PLoS One, Public Library of Science, Volume 8, Issue 6, JUN 2013, e65734|
|Keywords: ||prostate cancer|
|Abstract: ||Oxysterols are oxidation products of cholestane-3β, 5α, 6β-triol (abbreviated|
as triol) is one of the most abundant and active oxysterols. Here, we report that triol exhibits
anti-cancer activity against human prostate cancer cells. Treatment of cells with triol
dose-dependently suppressed proliferation of LNCaP CDXR-3, DU-145, and PC-3 human
prostate cancer cells and reduced colony formation in soft agar. Oral administration of triol at 20
mg/kg daily for three weeks significantly retarded the growth of PC-3 xenografts in nude mice.
Flow cytometric analysis revealed that triol treatment at 10-40 μM caused G1 cell cycle arrest
while the TUNEL assay indicated that triol treatment at 20-40 μM induced apoptosis in all three
cell lines. Micro-Western Arrays and traditional Western blotting methods indicated that triol
treatment resulted in reduced expression of Akt1, phospho-Akt Ser473, phospho-Akt Thr308,
PDK1, c-Myc, and Skp2 protein levels as well as accumulation of the cell cycle inhibitor p27Kip.
Triol treatment also resulted in reduced Akt1 protein expression in PC-3 xenografts.
Overexpression of Skp2 in PC-3 cells partially rescued the growth inhibition caused by triol.
Triol treatment suppressed migration and invasion of DU-145, PC-3, and CDXR-3 cells. The
expression levels of proteins associated with epithelial-mesenchymal transition as well as focal
adhesion kinase were affected by triol treatment in these cells. Triol treatment caused increased
expression of E-cadherin protein levels but decreased expression of N-cadherin, vimentin, Slug,
FAK, phospho-FAK Ser722, and phospho-FAK Tyr861 protein levels. Confocal laser
microscopy revealed redistribution of beta-actin and alpha-tubulin at the periphery of the CDXR-3 and
DU-145 cells. Our observations suggest that triol may represent a promising therapeutic agent
for advanced metastatic prostate cancer.
|Relation Link: ||http://www.plos.org/|
|Appears in Collections:||[腦科學研究中心] 期刊論文|
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