6-Gingerol Induces Cell Cycle Arrest and Cell Death of Mutant p53-expressing Pancreatic Cancer Cells.
10.3349/ymj.2006.47.5.688
- Author:
Yon Jung PARK
1
;
Jing WEN
;
Seungmin BANG
;
Seung Woo PARK
;
Si Young SONG
Author Information
1. Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
[6]-gingerol;
pancreatic cancer;
G1 phase;
apoptosis;
AKT
- MeSH:
Tumor Suppressor Protein p53/*genetics/metabolism;
Proto-Oncogene Proteins c-akt/genetics/metabolism;
Pancreatic Neoplasms/*drug therapy;
Mutation;
Humans;
Gene Expression Regulation, Neoplastic/drug effects;
Fatty Alcohols/*pharmacology/therapeutic use;
Drug Resistance, Neoplasm;
Cell Proliferation/drug effects;
Cell Line, Tumor;
Cell Cycle/*drug effects;
Apoptosis/*drug effects;
Antineoplastic Agents/*pharmacology/therapeutic use
- From:Yonsei Medical Journal
2006;47(5):688-697
- CountryRepublic of Korea
- Language:English
-
Abstract:
[6]-Gingerol, a major phenolic compound derived from ginger, has anti-bacterial, anti-inflammatory and anti-tumor activities. While several molecular mechanisms have been described to underlie its effects on cells in vitro and in vivo, the underlying mechanisms by which [6]-gingerol exerts anti-tumorigenic effects are largely unknown. The purpose of this study was to investigate the action of [6]-gingerol on two human pancreatic cancer cell lines, HPAC expressing wild- type (wt) p53 and BxPC-3 expressing mutated p53. We found that [6]-gingerol inhibited the cell growth through cell cycle arrest at G1 phase in both cell lines. Western blot analyses indicated that [6]-gingerol decreased both Cyclin A and Cyclin-dependent kinase (Cdk) expression. These events led to reduction in Rb phosphorylation followed by blocking of S phase entry. p53 expression was decreased by [6]-gingerol treatment in both cell lines suggesting that the induction of Cyclin-dependent kinase inhibitor, p21(cip1), was p53-independent. [6]-Gingerol induced mostly apoptotic death in the mutant p53-expressing cells, while no signs of early apoptosis were detected in wild type p53-expressing cells and this was related to the increased phosphorylation of AKT. These results suggest that [6]-gingerol can circumvent the resistance of mutant p53- expressing cells towards chemotherapy by inducing apoptotic cell death while it exerts cytostatic effect on wild type p53- expressing cells by inducing temporal growth arrest.
