title: Potentiation by BL191 of differentiation of neuroblastoma cells induced by dibutyryl cAMP and prostaglandin E(1).
abstract: BL191, a newly developed phosphodiesterase inhibitor, markedly potentiated a differentiation of neuroblastoma cell clones (Neuro2a, NS-20Y, and N1E115) induced by dibutyryl cyclic adensoine 3?:5?-monophosphate(dibutyryl cAMP) and prostaglandin E(1) (PGE(1)). BL191 (1 mM) inhibited DNA synthesis more strongly when used together with PGE(1) (0.5 ?g/ml) and dibutyryl cAMP (0.5 mM) than papaverine (1.6 ?g/ml) alone did. The inhibition rates of DNA synthesis were 72.5% for N1E-115, 75.3% for Neuro2a, and 82.5% for NS-20Y. After the treatment with BL191. PGE(1), and dibutyryl cAMP for 48 h all of three cell lines became enlarged and flattened, and extended long processes. The specific activities of choline acetyl transferase (EC 2.3.1.9) of NS-20Y and dopamine ?-hydroxylase (EC 1.14.17.1) of N1E-115 increased about 3-fold as compared to the controls. The tumorigenicities of Neuro2a and N1E-115 cells were decreased, but not of NS-20Y. These data suggest the heterogenous responsiveness in neuroblastoma cells to drug treatment.
authors.affiliation: Departments of Surgery (2nd Division) and Biochemistry (1st Division), Nagoya City University Medical School, Mizuho-Ku, Nagoya 467, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: T
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authors.lastname: Kato
authors.forename: Y
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authors.lastname: Sakazaki
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authors.initials: Y
authors.lastname: Yamakawa
authors.forename: N
authors.initials: N
authors.lastname: Naganawa
authors.forename: J
authors.initials: J
authors.lastname: Funabiki
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: R
authors.initials: R
authors.lastname: Tanaka
authors.forename: A
authors.initials: A
authors.lastname: Masaoka
authors.forename: H
authors.initials: H
authors.lastname: Tsunooka