[6]-Gingerol Induces Cell Cycle Arrest and Cell Death of Mutant p53-expressing Pancreatic Cancer Cells

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 wildtype (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 p53expressing cells towards chemotherapy by inducing apoptotic cell death while it exerts cytostatic effect on wild type p53expressing cells by inducing temporal growth arrest.