Malíková Jana, Swaczynová Jana, Kolár Zdenek, Strnad Miroslav
Laboratory of Molecular Pathology, Institute of Pathology, Faculty of Medicine, Palacký University, Hnevotínská 3, 775 15 Olomouc, Czech Republic.
Phytochemistry. 2008 Jan;69(2):418-26. doi: 10.1016/j.phytochem.2007.07.028. Epub 2007 Sep 14.
Brassinosteroids (BRs) are steroid plant hormones that are essential for many plant growth and developmental processes, including cell expansion, vascular differentiation and stress responses. Up to now the inhibitory effects of BRs on cell division of mammalian cells are unknown. To determine basic anticancer structure-activity relationships of natural BRs on human cells, several normal and cancer cell lines have been used. Several of the tested BRs were found to have high cytotoxic activity. Therefore, in our next series of experiments, we tested the effects of the most promising and readily available BR analogues with interesting anticancer properties, 28-homocastasterone (1) and 24-epibrassinolide (2), on the viability, proliferation, and cycling of hormone-sensitive/insensitive (MCF-7/MDA-MB-468) breast and (LNCaP/DU-145) prostate cancer cell lines to determine whether the discovered cytotoxic activity of BRs could be, at least partially, related to brassinosteroid-nuclear receptor interactions. Both BRs inhibited cell growth in a dose-dependent manner in the cancer cell lines. Flow cytometry analysis showed that BR treatment arrested MCF-7, MDA-MB-468 and LNCaP cells in G(1) phase of the cell cycle and induced apoptosis in MDA-MB-468, LNCaP, and slightly in the DU-145 cells. Our results provide the first evidence that natural BRs can inhibit the growth, at micromolar concentrations, of several human cancer cell lines without affecting the growth of normal cells. Therefore, these plant hormones are promising leads for potential anticancer drugs.
油菜素甾醇（BRs）是一类甾体植物激素，对许多植物生长和发育过程至关重要，包括细胞扩张、维管分化和应激反应。到目前为止，BRs对哺乳动物细胞分裂的抑制作用尚不清楚。为了确定天然BRs对人类细胞的基本抗癌构效关系，使用了几种正常和癌细胞系。发现几种受试BRs具有高细胞毒活性。因此，在我们接下来的一系列实验中，我们测试了最有前景且易于获得的具有有趣抗癌特性的BR类似物，28-高表油菜素内酯（1）和24-表油菜素内酯（2），对激素敏感/不敏感的（MCF-7/MDA-MB-468）乳腺癌和（LNCaP/DU-145）前列腺癌细胞系的活力、增殖和细胞周期的影响，以确定所发现的BRs的细胞毒活性是否至少部分与油菜素甾醇-核受体相互作用有关。两种BRs均以剂量依赖方式抑制癌细胞系中的细胞生长。流式细胞术分析表明，BR处理使MCF-7、MDA-MB-468和LNCaP细胞停滞在细胞周期的G(1)期，并诱导MDA-MB-468、LNCaP细胞凋亡，DU-145细胞有轻微凋亡。我们的结果提供了首个证据，即天然BRs在微摩尔浓度下可抑制几种人类癌细胞系的生长，而不影响正常细胞的生长。因此，这些植物激素有望成为潜在抗癌药物的先导物。
