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Curcumin suppresses proliferation and invasion in human gastric cancer cells by downregulation of PAK1 activity and cyclin D1 expression.
- Source :
-
Cancer biology & therapy [Cancer Biol Ther] 2009 Jul; Vol. 8 (14), pp. 1360-8. Date of Electronic Publication: 2009 Jul 13. - Publication Year :
- 2009
-
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 downregulated the mRNA and the protein expression of cyclin D1 and suppressed transition of the cells from G(1) 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.
- Subjects :
- Cell Division drug effects
Cell Line, Tumor drug effects
Cell Line, Tumor enzymology
Cell Line, Tumor pathology
Cyclin D1 genetics
Down-Regulation drug effects
Drug Screening Assays, Antitumor
Genes, erbB-2 drug effects
Humans
Neoplasm Invasiveness prevention & control
Neoplasm Proteins genetics
Receptor, ErbB-2 biosynthesis
p21-Activated Kinases genetics
Adenocarcinoma pathology
Anticarcinogenic Agents pharmacology
Curcumin pharmacology
Cyclin D1 biosynthesis
Gene Expression Regulation, Neoplastic drug effects
Neoplasm Proteins biosynthesis
Protein Kinase Inhibitors pharmacology
Stomach Neoplasms pathology
p21-Activated Kinases biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1555-8576
- Volume :
- 8
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Cancer biology & therapy
- Publication Type :
- Academic Journal
- Accession number :
- 19448398
- Full Text :
- https://doi.org/10.4161/cbt.8.14.8720