Cyclic nucleotides and neuroblastoma differentiation.
We have shown that intracellular cGMP levels increase during retinoic acid- and mycophenolic acid-induced neuroblastoma differentiation and that a 6 days treatment with 1 mM dbcGMP lead LAN5 cell to elaborate a network of neuritic processes suggesting an involvement of cGMP in neuroblastoma differentiation. We have also investigated the effects of some specific inhibitors of phosphodiesterases (PDE1, PDE3, PDE4 and PDE5) on human neuroblastoma (LAN5 and SHEP) growth and differentiation. After six days of incubation in the presence of each specific inhibitor at 10 x IC50 levels a cytostatic and differentiating effect was only observed with the PDE5 inhibitors Zaprinast and MY-5445. The cytostatic effect of these compounds increased increasing their concentrations far above their IC50 levels for PDE5, suggesting that these compounds could act by interfering with other molecular events than direct cGMP-PDE inhibition. No appreciable effect was observed using Dipyridamole, another specific PDE5 inhibitor.
Messina
E
E
Department of Experimental Medicine and Pathology, La Sapienza University, Rome, Italy.
Lupi
F
F
Barile
L
L
Giacomello
A
A
D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004176:Dipyridamole / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology*; D009712:Nucleotides, Cyclic / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010793:Phthalazines / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D013997:Time Factors
D004791:Enzyme Inhibitors; D009712:Nucleotides, Cyclic; D010726:Phosphodiesterase Inhibitors; D010793:Phthalazines; D011688:Purinones; D004176:Dipyridamole; D000242:Cyclic AMP; C052490:MY 5445; C011145:zaprinast; D006152:Cyclic GMP