Biological Sciences Division
Published June 13, 2013 | Version v1
Journal article Open

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

Creators

  • 1. National Health Research Institutes
  • 2. Mackay Memorial Hospital
  • 3. University of Chicago
  • 4. National Central University
  • 5. Taoyuan Armed Forces General Hospital
  • 6. National Tsing Hua University

Description

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 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 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.

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journal.pone.0065734.pdf

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Additional details

Identifiers

DOI
10.1371/journal.pone.0065734
Other
oai:uchicago.tind.io:10893

Funding

National Health Research Institutes
CS-101-PP-14
National Science Council in Taiwan
99-2320-B-400-015-MY3
National Science Council in Taiwan
101-2325-B-400-014
Department of Health in Taiwan
DOH101-TD-C-111-004

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Accounting, Ben May Department for Cancer Research, Genetics, Genomics, and Systems Biology