Caudatin inhibits carcinomic human alveolar basal epithelial cell growth and angiogenesis through modulating GSK3β/β-catenin pathway

Abstract

In this study, we investigate the anti-cancer activity of caudatin in carcinomic human alveolar basal epithelial cell line A549 and anti-angiogenic activity in human umbilical vein endothelial cells (HUVECs). We show that caudatin impairs the cell viability and induces G(0) /G(1) phase arrest in A549 cells with a dose dependent manner. A549 cells, not HUVECs, dealing with caudatin exhibited typical characteristics of apoptosis, which were accompanied by activation of caspase-3, caspase-9 and Poly(ADP-Ribose) Polymerase (PARP). In addition, caudatin treatment resulted in a decrease of β-catenin and increase of phosphorylation of β-catenin, and inhibited phosphorylation levels of GSK3β (Ser 9) in A549 cells. Conditional medium of A549 cells-induced or growth factors-induced tube formation of HUVECs was markedly inhibited by caudatin treatment, which was associated with the inhibiting VEGF secretion from A549 cells by caudatin. Our findings suggest that caudatin inhibits carcinomic human alveolar basal epithelial cell growth and angiogenesis by targeting GSK3β/β-catenin pathway and suppressing VEGF production.