Laboratory of Molecular Pathology, Department of Clinical and Molecular Pathology, Faculty of Medicine and Dentistry, Palacký University, Hněvotínská 3, 775 15 Olomouc, Czech Republic.
Food Chem Toxicol. 2012 Nov;50(11):4068-76. doi: 10.1016/j.fct.2012.08.031. Epub 2012 Aug 23.
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 antiproliferative 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.
油菜素甾醇（BRs）是一组多羟基甾醇衍生物，在各种植物生理过程中具有重要的调节作用。本研究旨在研究天然 BRs 28-高同型 castasterone（28-homoCS）和 24-表油菜素内酯（24-epiBL）在激素敏感和不敏感（LNCaP 和 DU-145，分别）人前列腺癌细胞系中的抗增殖活性的机制。通过流式细胞术、Western blot、TUNEL、DNA 梯状分析和免疫荧光分析研究了 BRs 对前列腺癌细胞的影响。研究的 BRs 抑制 LNCaP 细胞的生长并诱导 G1 期阻滞，伴随 cyclin D1、CDK4/6 和 pRb 表达减少。BR 处理 DU-145 细胞后，观察到细胞周期 G2/M 期的细胞比例增加，同时 cyclins A 和 B1 下调。通过免疫荧光分析显示 BR 处理后 LNCaP 细胞中 AR 定位模式的变化。此外，凋亡检测方法表明 BRs 在两种细胞系中均诱导凋亡，但在每种细胞系中，凋亡相关蛋白的表达变化由 28-homoCS 和 24-piBL 以不同的方式调节。研究的 BRs 似乎具有很强的生长抑制和促凋亡作用，因此可能是前列腺癌抗癌药物的极具价值的新候选药物。
