Deltonin Isolated from Dioscorea zingiberensis Inhibits Cancer Cell Growth through Inducing Mitochondrial Apoptosis and Suppressing Akt and Mitogen Activated Protein Kinase Signals

Abstract

Deltonin is an active component purified from Dioscorea zingiberensis WRIGHT (DZW), and has shown anticancer effects. However, its mechanism of action remains elusive. In the present study, we investigated the effect of Deltonin on a panel of cancer cell lines and analyzed its mechanism in C26 cells, a murine colon carcinoma cell. Our results showed that Deltonin markedly inhibited the growth of all examined cancer cell lines. Deltonin induced dose- and time-dependent apoptosis in C26 cells. The event of apoptosis was accompanied by the release of cytochrome c, depolarization of mitochondrial membrane potential, and dose- and time-dependent reactive oxygen species (ROS) generation. Deltonin also increased the expression of Bax, decreased the expression of B-cell lymphoma/lewkmia-2 (Bcl-2), and induced the activation of caspase 9, caspase 3 and poly(ADP-ribose) polymerase (PARP). Furthermore, Deltonin decreased Akt and extracellular signal-regulated kinase-1/2 (ERK_1/2) activity. These results demonstrate that Deltonin mediates the growth inhibition of cancer cells through multiple targets, which include the generation of reactive oxygen species (ROS), mitochondrial apoptosis and the inhibition of the mitogen-activated protein kinase (MAPK) and Akt signaling pathways, suggesting Deltonin is a potent cancer preventive and therapeutic agent.