Phosphodiesterase type III inhibitor, cilostazol, inhibits colon cancer cell motility

Clin Exp Metastasis. 1999;17(6):525-30. doi: 10.1023/a:1006626529536.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cell Movement / drug effects*
  • Cilostazol
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / pathology*
  • Humans
  • Phosphodiesterase Inhibitors / pharmacology*
  • Phosphoric Diester Hydrolases / drug effects*
  • Tetrazoles / pharmacology*
  • Tumor Cells, Cultured


  • Phosphodiesterase Inhibitors
  • Tetrazoles
  • Phosphoric Diester Hydrolases
  • Cilostazol