Curcumin suppresses proliferation and invasion in human gastric cancer cells by down-regulation of PAK1 activity and cyclin D1 expression

Abstract

Curcumin (diferuloylmethane), is a natural chemopreventive agent

known to inhibit the proliferation of several cancer cell lines. It has been

previously demonstrated that curcumin is a potent inhibitor of

EGF-receptor (EGFR) tyrosine kinase, but its inhibitive effect on

p21-activated kinase 1 (PAK1), a downstream protein of EGFR, has not

been defined. In this paper we found that curcumin repressed the

expression of HER2 and inhibited the kinase activity of PAK1 without

affecting its expression. Silencing HER2 in gastric cancer cells showed

that even if PAK1 activity was transiently strengthened by EGF, curcumin

still had a strong inhibitive effect. It should be emphasized that kinase

assay in vitro showed that curcumin could act as an ATP-competitive

inhibitor, which was supported by computer-aided molecular modeling.

Curcumin also down-regulated the mRNA and the protein expression of

cyclin D1 and suppressed transition of the cells from G1 to S phase.

Therefore, curcumin inhibited the proliferation and invasion of gastric

cancer cells. Overall, these results provided novel insights into the

mechanisms of curcumin inhibition of gastric cancer cell growth and

potential therapeutic strategies for gastric cancer.