Cassane-type diterpenes from Caesalpinia minax induce apoptosis in pituitary adenoma: structure–activity relationship, ER stress and Wnt/β-catenin pathways.

Plant-derived natural products have been the highly significant sources of novel antitumor agents. The cassane-type diterpenes of genusCaesalpiniahave been reported to bear antiproliferative activities toward different types of cancer cells. In this study, we evaluated the antineoplasmic activities of 16 natural origin cassane-type diterpenes isolated from the CHCl3extract of the seeds ofC. minaxin pituitary adenomas cells and identified caesalpin G (CAG) showed the strongest cytotoxicity. Moreover, we further investigated the structure–activity relationship and molecular mechanism of these derivatives systematically. The results confirmed the unsaturated lactone-type ring, hydroxyl at C-7, and alkenyl at C-11 or C-14 functionality as critical for anticancer activity in this family of natural products. In addition, the mechanism experiments also demonstrated unfolded protein response and ER stress and Wnt/β-catenin pathway were involved in the CAG-induced apoptosis. [ABSTRACT FROM PUBLISHER]