Steroids

Head of Research Program: Jana Oklešťková

 

steroidsThe steroids group focuses on the synthesis and study of the biological and immunological activities of brassinosteroids, plant and animal steroids and related compounds.

Brassinosteroids are involved in the control of many important physiological and developmental processes but their concentrations in plants are extremely low (pg.g-1 fresh weight, FW). For several years we have studied brassinosteroid structure-activity relationships. We endeavour  to generate a library of available and/or synthesable brassinosteroid- like ligands and dock the prepared library into BRI1 crystal structure and evaluate their biological activities in both plant and animal systems.  The biological activities of BR analogues in planta can be evaluated in two bioassays: the bean second internode bioassay and the pea inhibition bioassay. With international cooperation, we will be able to study BRI1-ligand-BAK1 interactions in vitro and the brassinosteroid receptor and co-receptor interaction based on fluorescent brassinosteroid probes. Progress in plant steroid chemistry and biology would have been impossible without specific sensitive methods for their detection in plant tissues. A series of polyclonal and monoclonal antibodies against brassinosteroids and vertebrate-type steroid hormones have been also developed and used in ELISA tests for detection of steroids in body fluids (e.g. cow milk) and for immunoaffinity chromatography (IAC). The combination of IAC with UHPLC/MS/MS can be used for determination of steroids in various plant species.

The cytotoxic effect of natural brassinosteroids and their synthetic analogues on human cancer cells derived from tumours were recently determined in vitro. The cellular and molecular mechanisms of action of these phytohormones in human cells remain unknown. Both natural brassinosteroids and their synthetic analogues could inhibit proliferation of human cancer cells, causing changes in the cell cycle/ apoptosis.

Angiogenesis, the growth of new blood vessels in animals is essential for organ growth as well as for growth of solid tumours and metastasis. Tumour angiogenesis targeting in the sense of discovery of novel drugs includes inhibition of proteolytic enzymes that break down the extracellular matrix surrounding existing capillaries, inhibition of endothelial cell proliferation, migration and enhancement of tumour endothelial cell apoptosis. Potent angiogenic inhibitors capable of blocking tumour growth may have potential for the development of novel generations of anticancer drugs. Brassinosteroids and their derivatives also could inhibit proliferation, migration and tube formation of human endothelial cells HUVEC (Human Umbilical Vein Endothelial Cells). The cellular and molecular mechanisms of action of these phytohormones in human cells are still unknown. Our results suggest that tested brassinosteroids are promising leads for the development of a new generation of potential anticancer drugs.