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 cell 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 inhibitors for those PDEs were used to determine which PDE is responsible for cAMP 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 cellular motility, we utilized chemotaxis assay. EHNA and zaprinast did not suppress serum-induced chemotaxis. In contrast, rolipram and Ro-20-1724, suppressed chemotaxis in a dose dependent fashion. These suggest that PDE 4 plays a critical role in regulating intracellular cAMP levels of colon cancer cells and is involved in cancer invasion. PDE 4 can be a novel target of anti-invasion drug.
Murata
K
K
Department of Surgical Oncology, Osaka Medical Center for Cancer and CVD, Higashinari, Japan. kmurata@yo.rim.or.jp
Sudo
T
T
Kameyama
M
M
Fukuoka
H
H
Muka
M
M
Doki
Y
Y
Sasaki
Y
Y
Ishikawa
O
O
Kimura
Y
Y
Imaoka
S
S
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D000242:Cyclic AMP / Q000096:biosynthesis; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004305:Dose-Response Relationship, Drug; D009361:Neoplasm Invasiveness; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4