The novel brassinosteroid analog BR4848 inhibits angiogenesis in human endothelial cells and induces apoptosis in human cancer cells in vitro.

摘要: We report the synthesis and detailed biological study of synthetic brassinosteroid analog 2α,3α-dihydroxy-6-oxo-5α-androstan-17β-yl N-(tert-butoxycarbonyl)-D,L-valinate (BR4848). The panel cancer cell lines was used for characterization its antiproliferative activity, yet had no adverse effects in normal human fibroblasts. In HeLa cells, BR4848-induced apoptosis accompanied by increase apoptotic subG1 PARP-1 caspase-7 fragmentation, downregulation Bcl-2 Mcl-1, an caspase activity G2/M phase cycle arrest. Antiproliferative properties BR4848 were exhibited inhibition phosphorylation Akt, Erk1/2 FAK. Furthermore, developed vitro antiangiogenic umbilical vein endothelial cells (HUVECs). with arrest detected cells. also inhibited adhesion, tube formation migration FAK, Erk 1/2, CDK5, VEGFR2, TNFα-stimulated production IL-6, angiopoietin-2 Jagged1. Finally, did not modulate nor nuclear translocation any steroid receptors (ERα, ERβ, AR, MR PR) included reporter cell-based assays, which excludes genomic as a contributing factor to observed activities BR4848.