Antimetastatic effects of Terminalia catappa L. on oral cancer via a down-regulation of metastasis-associated proteases.
The incidence and mortality of oral cancer in Taiwan have been increased during the last decade, which could be mainly resulted from the difficulty in treatment related to metastasis. As a potential and popular folk medicine, Terminalia catappa leaves have been proven to possess various biological benefits including anti-cancer activities. However, the detailed effects and molecular mechanisms of T. catappa leaves on the metastasis of oral cancer cells were still unclear. Thus, SCC-4 oral cancer cells were subjected to a treatment with ethanol extracts of T. catappa leaves (TCE) and then analyzed for the effect of TCE on the migration and invasion. Modified Boyden chamber assays revealed that TCE treatment significantly inhibited the cell migration/invasion capacities of SCC-4 cells. Furthermore, results of zymography and western blotting showed that activities and protein levels of MMP-2, MMP-9 and u-PA were all inhibited by TCE. Further studies indicated that TCE may inhibit phosphorylation of ERK1/2, JNK1/2 and Akt while the expression of nuclear protein NF-kappaB, c-Jun and c-Fos were inhibited as well. EMSA assay revealed that the DNA-binding activity with AP-1 and NF-kappaB was also decreased by TCE. In conclusion, TCE may serve as a powerful chemopreventive agent against oral cancer metastasis.
Yang
Shun-Fa
SF
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Chen
Mu-Kuan
MK
Hsieh
Yih-Shou
YS
Yang
Jia-Sin
JS
Zavras
Athanasios-I
AI
Hsieh
Yih-Hsien
YH
Su
Shih-Chi
SC
Kao
Te-Yu
TY
Chen
Pen-Ni
PN
Chu
Shu-Chen
SC
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D054443:Cell Migration Assays; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000503:physiopathology; D010447:Peptide Hydrolases / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D029766:Terminalia / Q000737:chemistry*; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014062:Tongue Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology
D016588:Anticarcinogenic Agents; D010936:Plant Extracts; D013778:Tetrazolium Salts; D013844:Thiazoles; D010447:Peptide Hydrolases; C022616:thiazolyl blue