Cholestane-3β, 5α, 6β-triol Suppresses Proliferation, Migration, and Invasion of Human Prostate Cancer Cells

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Title:	Cholestane-3β, 5α, 6β-triol Suppresses Proliferation, Migration, and Invasion of Human Prostate Cancer Cells
Authors:	高永旭;Lin, Ching-Yu;Huo, Chieh;Kuo, Li-Kuo;Hiipakka, Richard A.;Jones, Richard Baker;Lin, Hui-Ping;Hung, Yuwen;Su, Liang-Cheng;Tseng, Jen-Chih;Kuo, Ying-Yu;Wang, Yu-Ling;Fukui, Yasuhisa;Kao, Yung-Hsi;Kokontis, John M.;Yeh, Chien-Chih;Chen, Linyi;Yang, Shiaw-Der;Fu, Hsiao-Hui;Chen, Ya-Wen;Tsai, Kelvin K. C.;Chang, Jang-Yang;Chuu, Chih-Pin
Contributors:	生醫理工學院生命科學系
Keywords:	Actin;Actins - metabolism;Agar;AKT protein;AKT1 protein;Androgens;Androgens - pharmacology;Animals;Anticancer properties;Antineoplastic Agents - pharmacology;Apoptosis;Apoptosis - drug effects;Armed forces;Biology;c-Myc protein;Cancer;Cancer therapies;Cell cycle;Cell Line, Tumor;Cell Movement - drug effects;Cell proliferation;Cell Proliferation - drug effects;Cellular biology;Chemical compounds;Cholestanols - pharmacology;Cholesterol;Disease Models, Animal;E-cadherin;Epithelial-Mesenchymal Transition - drug effects;Flow cytometry;Focal adhesion kinase;G1 Phase Cell Cycle Checkpoints - drug effects;Gene Expression;Hospitals;Humans;Kinases;Laser microscopy;Life sciences;Liver X Receptors;Male;Medical research;Medicine;Mens health;Mesenchyme;Metastases;Metastasis;Mice;Microscopy;Mouse devices;Myc protein;N-Cadherin;Neoplasm Invasiveness;Oral administration;Orphan Nuclear Receptors - agonists;Oxidation;Pharmacology;Phosphorylation;Prostate cancer;Prostatic Neoplasms - genetics;Prostatic Neoplasms - metabolism;Prostatic Neoplasms - pathology;Proteins;Proteome;Proto-Oncogene Proteins c-akt - metabolism;S-Phase Kinase-Associated Proteins - genetics;Signal Transduction;Skp2 protein;Surgery;Tubulin - metabolism;Tumor Burden - drug effects;Tumor Stem Cell Assay;Western blotting;Xenograft Model Antitumor Assays;Xenografts;Xenotransplantation
Date:	2013-06-13
Issue Date:	2026-04-23 11:12:07 (UTC+8)
Publisher:	Public Library of Science;United States: Public Library of Science
Abstract:	摘要： Oxysterols are oxidation products of cholesterol. 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 p27(Kip). 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 β-actin and α-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. 其他題名： PLoS One 出版者： United States: Public Library of Science 出版日期： 2013-06-13 出處： PloS one, 2013-06, Vol.8 (6), p.e65734 資源來源： ProQuest Agricultural & Environmental Science Database 版權： 2013 Lin et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 版權： 2013 Lin et al 2013 Lin et al 識別號： ISSN: 1932-6203 識別號： EISSN: 1932-6203 識別號： DOI: 10.1371/journal.pone.0065734 識別號： PMID: 23785446
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