α-Chaconine, a potato glycoalkaloid, induces apoptosis of HT-29 human colon cancer cells through caspase-3 activation and inhibition of ERK 1/2 phosphorylation

Although α-chaconine, one of the two major potato trisaccharide glycoalkaloids, have shown cytotoxic effects on human cancer cells, the exact mechanism of this action of α-chaconine is not completely understood. In this study, we found that α-chaconine induced apoptosis of HT-29 cells in a time- and concentration-dependent manner by using flow cytometric analysis. We also found that caspase-3 activity and the active form of caspase-3 were increased 12 h after α-chaconine treatment. Caspase inhibitors, N-Ac-DEVD-CHO and Z-VAD-fmk, prevented α-chaconine-induced apoptosis, whereas α-chaconine-induced apoptosis was potentiated by PD98059, an extracellular signal-regulated kinase (ERK) inhibitor. However, pretreatment of the cells with LY294002 and SB203580, inhibitors of PI3K and p38, respectively, BAPTA-AM, an intracellular Ca2+ chelator, and antioxidants such as N-acetylcysteine (NAC) and Trolox had no effect on the α-chaconine-induced cell death. In addition, phosphorylation of ERK was reduced by the treatment with α-chaconine. Moreover, α-chaconine-induced caspase-3 activity was further increased by the pretreatment with PD98059. Thus, the results indicate that α-chaconine induces apoptosis of HT-29 cells through inhibition of ERK and, in turn, activation of caspase-3.