Potentiation by BL191 of differentiation of neuroblastoma cells induced by dibutyryl cAMP and prostaglandin E(1).
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.
Kato
H
H
Departments of Surgery (2nd Division) and Biochemistry (1st Division), Nagoya City University Medical School, Mizuho-Ku, Nagoya 467, Japan.
Kato
T
T
Sakazaki
Y
Y
Yamakawa
Y
Y
Naganawa
N
N
Funabiki
J
J
Kato
T
T
Tanaka
R
R
Masaoka
A
A
Tsunooka
H
H