Multiple mechanisms are involved in 6‐gingerol‐induced cell growth arrest and apoptosis in human colorectal cancer cells
- 30 November 2007
- journal article
- research article
- Published by Wiley in Molecular Carcinogenesis
- Vol. 47 (3), 197-208
- https://doi.org/10.1002/mc.20374
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 β‐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 G1 cell cycle arrest. Subsequently, 6‐gingerol suppressed cyclin D1 expression and induced NAG‐1 expression. Cyclin D1 suppression was related to inhibition of β‐catenin translocation and cyclin D1 proteolysis. Furthermore, experiments using inhibitors and siRNA transfection confirm the involvement of the PKCε and glycogen synthase kinase (GSK)‐3β pathways in 6‐gingerol‐induced NAG‐1 expression. The results suggest that 6‐gingerol stimulates apoptosis through upregulation of NAG‐1 and G1 cell cycle arrest through downregulation of cyclin D1. Multiple mechanisms appear to be involved in 6‐gingerol action, including protein degradation as well as β‐catenin, PKCε, and GSK‐3β pathways.Keywords
This publication has 50 references indexed in Scilit:
- Protein kinase Cε and development of squamous cell carcinoma, the nonmelanoma human skin cancerMolecular Carcinogenesis, 2006
- Changes in gene expression contribute to cancer prevention by COX inhibitorsProgress in Lipid Research, 2006
- [6]-Gingerol, a pungent ingredient of ginger, inhibits angiogenesis in vitro and in vivoBiochemical and Biophysical Research Communications, 2005
- Indole-3-carbinol and 3,3′-diindolylmethane induce expression of NAG-1 in a p53-independent mannerBiochemical and Biophysical Research Communications, 2005
- Expression of NAG-1, a Transforming Growth Factor-β Superfamily Member, by Troglitazone Requires the Early Growth Response Gene EGR-1Online Journal of Public Health Informatics, 2004
- Cancer chemoprevention with dietary phytochemicalsNature Reviews Cancer, 2003
- Protein kinase Cɛ interacts with Bax and promotes survival of human prostate cancer cellsOncogene, 2003
- Gingerols: a novel class of vanilloid receptor (VR1) agonistsBritish Journal of Pharmacology, 2002
- Regulation of expression of the multidrug resistance protein MRP1 by p53 in human prostate cancer cellsJCI Insight, 2000
- Protein kinase C isoforms in the chemopreventive effects of a novel vitamin D3 analogue in rat colonic tumorigenesisGastroenterology, 1996