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

Abstract

Although alpha-chaconine, one of the two major potato trisaccharide glycoalkaloids, have shown cytotoxic effects on human cancer cells, the exact mechanism of this action of alpha-chaconine is not completely understood. In this study, we found that alpha-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 alpha-chaconine treatment. Caspase inhibitors, N-Ac-DEVD-CHO and Z-VAD-fmk, prevented alpha-chaconine-induced apoptosis, whereas alpha-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 Ca(2+) chelator, and antioxidants such as N-acetylcysteine (NAC) and Trolox had no effect on the alpha-chaconine-induced cell death. In addition, phosphorylation of ERK was reduced by the treatment with alpha-chaconine. Moreover, alpha-chaconine-induced caspase-3 activity was further increased by the pretreatment with PD98059. Thus, the results indicate that alpha-chaconine induces apoptosis of HT-29 cells through inhibition of ERK and, in turn, activation of caspase-3.

• Authors: Seun-Ah Yang, Seung-Hwan Paek, Nobuyuki Kozukue, Kap-Rang Lee, Jung-Ae Kim
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 44 Issue 6 Pg. 839-46 (Jun 2006) ISSN: 0278-6915 [Print] England
• PMID: 16387404 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Solanine
• alpha-chaconine
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• CASP3 protein, human
• Caspase 3
• Caspases

Topics

• Apoptosis (drug effects)
• Caspase 3
• Caspases (metabolism)
• Enzyme Activation (drug effects)
• Enzyme Inhibitors (pharmacology)
• HT29 Cells
• Humans
• Mitogen-Activated Protein Kinase 1 (antagonists & inhibitors, metabolism)
• Mitogen-Activated Protein Kinase 3 (antagonists & inhibitors, metabolism)
• Phosphorylation (drug effects)
• Solanine (analogs & derivatives, pharmacology)