Multiple mechanisms are involved in 6-gingerol-induced cell growth arrest and apoptosis in human colorectal cancer cells.

Abstract

6-Gingerol, a natural product of ginger, has been known to possess anti-tumorigenic and pro-apoptotic activities. However, the mechanisms by which it prevents cancer are not well understood in human colorectal cancer. Cyclin D1 is a proto-oncogene that is overexpressed in many cancers and plays a role in cell proliferation through activation by beta-catenin signaling. Nonsteroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1) is a cytokine associated with pro-apoptotic and anti-tumorigenic properties. In the present study, we examined whether 6-gingerol influences cyclin D1 and NAG-1 expression and determined the mechanisms by which 6-gingerol affects the growth of human colorectal cancer cells in vitro. 6-Gingerol treatment suppressed cell proliferation and induced apoptosis and G(1) cell cycle arrest. Subsequently, 6-gingerol suppressed cyclin D1 expression and induced NAG-1 expression. Cyclin D1 suppression was related to inhibition of beta-catenin translocation and cyclin D1 proteolysis. Furthermore, experiments using inhibitors and siRNA transfection confirm the involvement of the PKCepsilon and glycogen synthase kinase (GSK)-3beta pathways in 6-gingerol-induced NAG-1 expression. The results suggest that 6-gingerol stimulates apoptosis through upregulation of NAG-1 and G(1) cell cycle arrest through downregulation of cyclin D1. Multiple mechanisms appear to be involved in 6-gingerol action, including protein degradation as well as beta-catenin, PKCepsilon, and GSK-3beta pathways.

• Authors: Seong-Ho Lee, Maria Cekanova, Seung Joon Baek
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 47 Issue 3 Pg. 197-208 (Mar 2008) ISSN: 1098-2744 [Electronic] United States
• PMID: 18058799 (Publication Type: Journal Article)
• Copyright: (c) 2007 Wiley-Liss, Inc.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antineoplastic Agents
• Catechols
• Fatty Alcohols
• MAS1 protein, human
• Proto-Oncogene Mas
• beta Catenin
• Cyclin D1
• gingerol
• Luciferases

Topics

• Anti-Inflammatory Agents, Non-Steroidal (metabolism)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Caco-2 Cells
• Catechols
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colorectal Neoplasms (drug therapy, pathology)
• Cyclin D1 (metabolism)
• Dose-Response Relationship, Drug
• Fatty Alcohols (pharmacology)
• G1 Phase (drug effects)
• HT29 Cells
• Humans
• Luciferases (metabolism)
• Plasmids
• Proto-Oncogene Mas
• S Phase (drug effects)
• Statistics as Topic
• Transfection
• beta Catenin (metabolism)