zaprinast and Neuroblastoma
zaprinast has been researched along with Neuroblastoma* in 3 studies
Other Studies
3 other study(ies) available for zaprinast and Neuroblastoma
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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. Topics: Cell Differentiation; Cell Line, Tumor; Cell Proliferation; Cyclic AMP; Cyclic GMP; Dipyridamole; Dose-Response Relationship, Drug; Enzyme Inhibitors; Humans; Inhibitory Concentration 50; Neuroblastoma; Nucleotides, Cyclic; Phosphodiesterase Inhibitors; Phthalazines; Purinones; Time Factors | 2004 |
In vitro and in vivo inhibition of SK-N-MC neuroblastoma growth using cyclic nucleotide phosphodiesterase inhibitors.
The effect of cyclic nucleotide phosphodiesterase (PDE) inhibitors Zaprinast and DC-TA-46 has been tested on SK-N-MC neuroblastoma growth. Antiproliferative activity of the tested drugs was assayed both in vitro and in the xenograft model of nude mice. In clonal density experiments, the IC50 value was 3.3 microM for Zaprinast and 1.9 microM for DC-TA-46, while 7.5 microM BCNU alkylating agent was required to obtain the same effect. SK-N-MC cells xenografted in the nude mouse showed that the administration of Zaprinast and DC-TA-46 caused a significant 50% decrease of the tumour weight. These data demonstrate that PDE inhibitors may be useful for at least reducing tumour growth; they may be of interest for further evaluation as alternative molecules in the design of multiple agent protocols for neuroblastoma treatment. Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Animals; Antineoplastic Agents; Cell Division; Male; Mice; Mice, Nude; Neoplasm Transplantation; Neuroblastoma; Phosphodiesterase Inhibitors; Piperazines; Pteridines; Purinones; Tumor Cells, Cultured | 2001 |
Characterization of 3':5' cyclic nucleotide phosphodiesterase activities of mouse neuroblastoma N18TG2 cells.
Characterization of 'low Km' 3':5' cyclic nucleotide phosphodiesterase activities (PDE) expressed in mouse N18TG2 neuroblastoma cells is reported. At least 3 peaks of activity were isolated by DEAE chromatography, none of which was calcium-calmodulin stimulated and cGMP stimulated or inhibited. A first peak elutes at 200 mM sodium acetate; it specifically hydrolyzes cGMP with a Km of 4.7 microM and shows sensitivity to zaprinast [M&B 22948] (1.8 microM). A second peak eluting at 410 mM sodium acetate hydrolyzes both cyclic nucleotides. A third peak, specific for cAMP hydrolysis, elutes at 580 mM sodium acetate, has a Km of 3.2 microM and is sensitive to RO 20 1724 (7.6 microM) and rolipram (2 microM). Hydrodynamic analysis showed for the first peak a Stokes radius of 5.3 nm with a sedimentation coefficient of 8.1 S, a frictional ratio (f/fo) of 1.41 and a native molecular mass of 182 kDa. The same analysis for peak 3 showed a Stokes radius of 4.1 nm with a sedimentation coefficient of 3.2 S, a frictional ratio of 1.63 and a native molecular mass of 56 kDa. The biochemical features reported for the enzyme eluting in the first peak, and its cGMP-binding activity stimulated by inhibitors of phosphodiesterase activity, demonstrate that it belongs to the PDE V subfamily; on the other hand the cAMP specific enzyme eluting in the third peak can be assigned to the 'RO 20 1724 inhibited' form. The significance of these findings is discussed in relation to the functional characteristics of the N18TG2 cell line. Topics: 2',3'-Cyclic-Nucleotide Phosphodiesterases; Animals; Blood Platelets; Centrifugation, Density Gradient; Chromatography, DEAE-Cellulose; Chromatography, Gel; Cyclic GMP; Cytosol; Electrophoresis, Polyacrylamide Gel; Kinetics; Lung; Mice; Molecular Weight; Neuroblastoma; Purinones; Rats; Tumor Cells, Cultured | 1993 |