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.
Giorgi
M
M
Dipartimento di Biologia di Base e Applicata, Università dell'Aquila, L'Aquila, Italy.
Leonetti
C
C
Citro
G
G
Augusti-Tocco
G
G
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000473:pathology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011621:Pteridines / Q000494:pharmacology*; D011688:Purinones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011621:Pteridines; D011688:Purinones; C081896:7-benzylamino-6-chloro-2-piperazino-4-pyrrolidinopteridine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; C011145:zaprinast