Molecular mechanisms of brassinosteroid action and receptor interactions in human hormone-(in) dependent carcinoma cells

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) are plant growth regulators representing a group of newly-discovered agents with relatively wide-ranging effects in plants. Like steroid hormones in animals, structurally BRs consist of a cholesterol skeleton with various hydroxyl substitutions and functional groups required for biological activity. To date, over 70 BRs have been identified in 50 plant species and currently over 40 brassinosteroid metabolites and their conjugates are known. Natural BRs and their synthetic derivatives caused growth inhibition, cell cycle arrest and initiation of apoptosis in different human cancer cell lines. Based on the structural motifs of these agents, a possible explanation for their cytotoxic effects is that they may bind to steroid receptors. In hormone-sensitive cancer cells derived from breast and prostate carcinomas, BR treatment resulted in alterations of localization and expression of the steroid hormone receptors (ER-α, ER-ß, AR). The comparison of the effects of natural BRs and their analogues on steroid receptors, and detailed characterization of their influence on hormone-sensitive and hormone-insensitive human carci­nomas, could both provide extend fundamental knowledge of hormone-receptor interactions and have valuable medical applications.

This work was supported by grant LF_2015_008, L01304 and L01204.