Induction of G-phase cell cycle arrest and apoptosis in human breast and prostate cancer cells by natural brassinosteroids

The study of plant-derived compounds with effect at the molecular level has become an important approach in the selection of new agents with antitumour activity in humans. Brassinosteroids (BRs), polyhydroxylated sterol derivatives with close structural similarity to animal and insect steroid hormones are plant growth regulators representing a group of newly-discovered agents with relatively wide-ranging effects in plants. Based on the structural motifs, one putative explanation for their strongly cytotoxic effect is their binding to steroid receptors. In this study, we characterized the effect of natural BRs (28-homocastasterone and 24-epibrassinolide) on cell growth and apoptosis in human hormone-sensitive and hormone-insensitive breast and prostate carcinoma cells. The aim was to identify the processes associated with apop-tosis induction and hormone-independent status in these cancer cells. The agents inhibited cell growth in all cell lines and resulted in alterations in the cell cycle progression and levels of cell cycle related proteins. Using flow cytometry, we found that BRs can disturb cell cycling in breast and prostate cancer cells. The results showed that treatment with either 28-homocastasterone or 24-epibrassinolide induced blocks in the G1 phase of the cell cycle in the MCF-7, MDA-MB-468 and LNCaP cell lines, associated with decreased expression of cyclin D1 and pRb phosphorylation and induction of cyclin kinase inhibitors p21Waf1/Cip1 and p27Kip1. In hormone-dependent cells, BR treatment led to induction of apoptosis and resulted in alterations of localization and expression of the steroid hormone receptors (ER-a, ER-|3, AR). Based on our data, the effect of BRs can be compared to the effect of antagonists to steroid hormone receptors. Our results suggest that the tested BRs are promising leads in the development of a new generation of potential anticancer drugs.

This work was supported by MSM 6198959216.