title: Phosphodiesterase type III inhibitor, cilostazol, inhibits colon cancer cell motility.
abstract: 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.
authors.affiliation: Osaka Medical Center for Cancer and Cardiovascular Diseases, Department of Surgical Oncology, Japan. kmurata@yo.rim.or.jp
authors.forename: K
authors.initials: K
authors.lastname: Murata
authors.forename: M
authors.initials: M
authors.lastname: Kameyama
authors.forename: F
authors.initials: F
authors.lastname: Fukui
authors.forename: H
authors.initials: H
authors.lastname: Ohigashi
authors.forename: M
authors.initials: M
authors.lastname: Hiratsuka
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: T
authors.initials: T
authors.lastname: Kabuto
authors.forename: M
authors.initials: M
authors.lastname: Mukai
authors.forename: T
authors.initials: T
authors.lastname: Mammoto
authors.forename: H
authors.initials: H
authors.lastname: Akedo
authors.forename: O
authors.initials: O
authors.lastname: Ishikawa
authors.forename: S
authors.initials: S
authors.lastname: Imaoka
mesh_terms: 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
chemical_list: D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; D010727:Phosphoric Diester Hydrolases; D000077407:Cilostazol