Inhibitory effect of norcantharidin, a derivative compound from blister beetles, on tumor invasion and metastasis in CT26 colorectal adenocarcinoma cells.
Norcantharidin (NCTD), a potential anti-cancer drug, is the demethylated analog of cantharidin isolated from blister beetles. The present study investigated the effect of NCTD on tumor invasion and metastasis. A cytotoxicity assay of NCTD in CT26 colorectal adenocarcinoma cells showed a dose- and time-dependent decrease in cell viability. NCTD (50 microM)-treated CT26 cells not only showed an inhibited cell invasion of 65.6%, but also decreased the activity of matrix metalloproteinase-2 and -9. NCTD decreased the adhesive ability of CT26 cells in a dose-dependent manner. At a concentration of 100 microM, NCTD showed a down-expression of several cadherin-catenin adhesion molecules, including Desmoglein, N-cadherin, and alpha- and beta-catenin, while there were no obvious changes in E-cadherin and gamma-catenin. Intraperitoneal injection of NCTD (2 mg/kg/day) in BALB/c mice reduced both the pulmonary metastatic capacity of CT26 cells and prolonged the survival day of the mice. These results demonstrated that it was effective in blocking both tumor invasion and metastasis.
Chen
Yu-Jen
YJ
Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan.
Shieh
Chwen-Jen
CJ
Tsai
Tung-Hu
TH
Kuo
Cheng-Deng
CD
Ho
Low-Tone
LT
Liu
Tsung-Yun
TY
Liao
Hui-Fen
HF
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology* / Q000627:therapeutic use; D002448:Cell Adhesion / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D008175:Lung Neoplasms / Q000517:prevention & control*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000517:prevention & control; D014407:Tumor Cells, Cultured
D019086:Bridged Bicyclo Compounds, Heterocyclic; D061965:Matrix Metalloproteinase Inhibitors; C069741:norcantharidin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9