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

摘要: Oxysterols are oxidation products of cholesterol. Cholestane-3β, 5α, 6β-triol (abbreviated as triol) is one the most abundant and active oxysterols. Here, we report that triol exhibits anti-cancer activity against human prostate cancer cells. Treatment cells with dose-dependently suppressed proliferation LNCaP CDXR-3, DU-145, PC-3 reduced colony formation in soft agar. Oral administration at 20 mg/kg daily for three weeks significantly retarded growth xenografts nude mice. Flow cytometric analysis revealed treatment 10–40 µM caused G1 cell cycle arrest while TUNEL assay indicated 20–40 induced apoptosis all lines. Micro-Western Arrays traditional Western blotting methods resulted expression Akt1, phospho-Akt Ser473, Thr308, PDK1, c-Myc, Skp2 protein levels well accumulation inhibitor p27Kip. Triol also Akt1 xenografts. Overexpression partially rescued inhibition by triol. migration invasion PC-3, CDXR-3 The proteins associated epithelial-mesenchymal transition focal adhesion kinase were affected these increased E-cadherin but decreased N-cadherin, vimentin, Slug, FAK, phospho-FAK Ser722, Tyr861 levels. Confocal laser microscopy redistribution β-actin α-tubulin periphery DU-145 Our observations suggest may represent a promising therapeutic agent advanced metastatic cancer.