Phosphodiesterase type III inhibitor, cilostazol, inhibits colon cancer cell motility.
Metastasis of cancer cells is initiated by the cellular migration into extracellular matrix and surrounding vessels. We previously showed that elevation of cAMP levels in cancer cells suppressed trans-cellular migration in vitro. Drugs that can elevate cAMP levels in cancer cells effectively may be applied to prevent metastasis in cancer patients. Cilostazol, an oral anti-platelet drug, is a specific cAMP phosphodiesterase type III inhibitor and has been clinically used to treat thrombosis patients. In chemotaxis assay, cellular migration of human colon cancer cells, DLD- 1, was induced by 10 microg/ml of soluble fibronectin or 10% of fetal bovine serum (FBS). Treatment with cilostazol (50 microM) suppressed 92.3% or 84.6% of the migration in control cells, respectively. When DLD-1 cells were stimulated by soluble fibronectin in phagokinetic assay, migration assessed by the area of gold particle phagocytosis track was induced and cilostazol also decreased 67.3% of the cellular migration in control cells. Furthermore, in the trans-cellular migration assay, cilostazol suppressed cancer cell invasion induced by FBS. Thus, cilostazol can suppress colon cancer cell motility and might be effective as an anti-metastasis drug for cancer patients.
Murata
K
K
Osaka Medical Center for Cancer and Cardiovascular Diseases, Department of Surgical Oncology, Japan. kmurata@yo.rim.or.jp
Kameyama
M
M
Fukui
F
F
Ohigashi
H
H
Hiratsuka
M
M
Sasaki
Y
Y
Kabuto
T
T
Mukai
M
M
Mammoto
T
T
Akedo
H
H
Ishikawa
O
O
Imaoka
S
S
D000818:Animals; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects*; D000077407:Cilostazol; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; D010727:Phosphoric Diester Hydrolases; D000077407:Cilostazol