Journal
FOOD AND CHEMICAL TOXICOLOGY
Volume 50, Issue 11, Pages 4068-4076Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2012.08.031
Keywords
Apoptosis; Brassinosteroids; Cell cycle; Hormone-sensitive/insensitive prostate cancer cells
Categories
Funding
- Ministry of Health of Czech Republic [IGA MZ CR NT11060]
- Centre of the Region Hana for Biotechnological and Agricultural Research [ED0007/01/01]
- Operational Programme Research and Development for Innovations [CZ.1.05/2.1.00/01.0030]
- [301/08/1649]
- [IAA400550801]
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Brassinosteroids (BRs) are a group of polyhydroxylated sterol derivatives with important regulatory roles in various plant physiological processes. The aim of this study was to examine the mechanism of the anti-proliferative activity of natural BRs 28-homocastasterone (28-homoCS) and 24-epibrassinolide (24-epiBL) in hormone-sensitive and -insensitive (LNCaP and DU-145, respectively) human prostate cancer cell lines. The effects of BRs on prostate cancer cells were surveyed using flow cytometry, Western blotting, TUNEL, DNA ladder assays and immunofluorescence analyses. The studied BRs inhibited cell growth and induced G(1) blocks in LNCaP cells accompanied by reductions in cyclin D-1, CDK4/6 and pRb expression. Following BR treatment of DU-145 cells, increases in proportions of cells in the G(2)/M phase of cell cycle were observed, accompanied by down-regulation of cyclins A and B-1. Changes in AR localization patterns in LNCaP cells treated with BRs were shown by immunofluorescence analysis. Furthermore, apoptotic detection methods demonstrated induction of apoptosis mediated by BRs in both cell lines, although changes in the expression of apoptosis-related proteins were modulated differently by 28-homoCS and 24-piBL in each cell line. The studied BRs seem to exert potent growth inhibitory and pro-apoptotic effects and could be therefore highly valuable new candidates for prostate anticancer drugs. (C) 2012 Elsevier Ltd. All rights reserved.
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