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

✍ Scribed by Seong-Ho Lee; Maria Cekanova; Seung Joon Baek

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 374 KB
• Volume: 47
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.20374

✦ Synopsis

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 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 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 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 β‐catenin, PKCε, and GSK‐3β pathways. © 2007 Wiley‐Liss, Inc.