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

Metastasis of cancer cells is initiated by the cellular migration into extr acellular matrix and surrounding vessels. We previously showed that elevati on of cAMP levels in cancer cells suppressed trans-cellular migration in vi tro. 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 m u g/ml of soluble fibronectin or 10% of fetal bovine serum (FBS). Treatment with cilostazol (50 mu M) suppressed 92.3% or 84.6% of the migration in co ntrol cells, respectively. When DLD-1 cells were stimulated by soluble fibr onectin in phagokinetic assay, migration assessed by the area of gold parti cle phagocytosis track was induced and cilostazol also decreased 67.3% of t he 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 effe ctive as an anti-metastasis drug for cancer patients.