Anti-metastasis effects of gallic acid on gastric cancer cells involves inhibition of NF-kappaB activity and downregulation of PI3K/AKT/small GTPase signals.
Polyphenols are natural antioxidants that are thought to contribute to prevention of cardiovascular disease and malignancy. Although many studies have been carried out to investigate the chemopreventive role of flavonoids, less attention has been focused on phenolic acids. In this study, the aim was to investigate the effect of phenolic acids found abundantly in vegetables, i.e. gallic acid (GA), caffeic acid (CA) and protocatechuic acid (PCA), on the inhibition of gastric adenocarcinoma (AGS) cell metastasis. The results showed 0.01 mM GA induced the same level of cell toxicity as 4.0mM PCA. Using wound-healing assay and Boyden chamber assay, GA had potent inhibitory effects on AGS cell migration. The expression of MMP-2/9 of AGS cells was inhibited by 2.0 microM of GA. It is possible that the suppressive effect of GA on MMP-2/9 might involve the inhibition of NF-kappaB activity. Multiple proteins involved in metastasis and the cytoskeletal reorganization signal pathway, including Ras, Cdc42, Rac1, RhoA, RhoB, PI3K and p38MAPK, were also inhibited by GA. Furthermore, immunoreactivity assay of cytoskeletal F-actin demonstrated a significant inhibitory effect of GA treatment. In conclusion, GA may have the potential to be an effective agent for prevention and treatment of gastric cancer metastasis.
Ho
Hsieh-Hsun
HH
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan.
Chang
Chi-Sen
CS
Ho
Wei-Chi
WC
Liao
Sheng-You
SY
Wu
Cheng-Hsun
CH
Wang
Chau-Jong
CJ
D000199:Actins / Q000378:metabolism; D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D005707:Gallic Acid / Q000494:pharmacology*; D006801:Humans; D062385:Hydroxybenzoates / Q000494:pharmacology; D047468:Immunoprecipitation; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology*; D014945:Wound Healing / Q000187:drug effects
D000199:Actins; D016588:Anticarcinogenic Agents; D002109:Caffeic Acids; D062385:Hydroxybenzoates; D016328:NF-kappa B; C009091:protocatechuic acid; D005707:Gallic Acid; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020559:Monomeric GTP-Binding Proteins; C040048:caffeic acid