Abstract
Molecular and cellular effects of two groups of antiproliferative agents, natural brassinosteroids (BRs) and their synthetic derivatives, were examined in different human cancer cell lines and in primary endothelial cells in vitro. Natural and synthetic BRs caused growth inhibition, cell cycle arrest and initiation of apoptosis in many different cancer cell lines. The inhibition of proliferation and migration of human endothelial cells by BRs was demonstrated and evidences were obtained that BRs initiate cell death by apoptosis. And, analogues of BRs were found to be more effective than natural BRs. Observed inhibition of migration and tube formation demonstrated the antiangiogenic activity of BRs. These findings indicate a potential use of BRs in the prevention of metastasis development. Investigation of the mechanisms of action of BRs in human cancer and endothelial cells using cellular and molecular techniques indicated the possible involvement of steroid receptors in BR action. However, BRs were shown not to bind directly to steroid receptors which demonstrate that BRs act via steroid receptor-independent pathway(s). Concluding, BRs and their derivatives are capable to inhibit growth of several human cancer cell lines and to inhibit angiogenesis-like behaviour of primary endothelial cells in vitro, as well.
Keywords: Antiangiogenic activity, anticancer drugs, apoptosis, breast cancer, metastasis development, cell cycle arrest.