Cyclic AMP specific phosphodiesterase activity and colon cancer cell motility

To investigate mechanisms for regulation of intracellular cAMP involved in cancer cell invasion, phosphodiesterase (PDE) activity in a colon cancer ce ll line, DLD-1, was studied. Activities of PDE 2, 4, and 5 were detected in DLD-1 cells by pharmacological approach. Specific and cell permeable inhib itors for those PDEs were used to determine which PDE is responsible for cA MP turnover involved in cancer cell motility. Treatment of DLD-1 cells with rolipram and Ro-20-1724, inhibitors for PDE 4, elevated intracellular cAMP contents three to five times of control. EHNA, an inhibitor for PDE 2, and zaprinast, an inhibitor for PDE 5, did not affect cAMP levels. To assess c ellular motility, we utilized chemotaxis assay. EHNA and zaprinast did not suppress serum-induced chemotaxis. In contrast, rolipram and Ro-20-1724, su ppressed chemotaxis in a dose dependent fashion. These suggest that PDE 4 p lays a critical role in regulating intracellular cAMP levels of colon cance r cells and is involved in cancer invasion. PDE 4 can be a novel target of anti-invasion drug.