Cell differentiation induced by poly(ADP-ribose) synthetase inhibitors.
From a survey of about 400 compounds, we found a number of potent and specific inhibitors of poly(ADP-ribose) synthetase. Two new classes of inhibitors include vesnarinones and heterocyclic amines. Although the inhibitory activity was not very strong, several of these classes of inhibitors proved to induce most efficiently differentiation of murine teratocarcinoma EC cells in culture; for example, 70 microM benzylvesnarinone or 1 mM PhIP effected almost complete change in cell morphology in 5 to 7 days. Analyses of poly(ADP-ribose) synthesis and NAD concentrations in EC cells after treatment with a differentiation inducer suggested that poly(ADP-ribose) might play a role at an initiation stage of cell differentiation.
Laboratory of Molecular Clinical Chemistry, Kyoto University, Japan.
K
K
Ueda
M
M
Banasik
S
S
Nakajima
H Y
HY
Yook
T
T
Kido
D000818:Animals; D002243:Carbolines / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011719:Pyrazines; D011804:Quinolines / Q000494:pharmacology; D013329:Structure-Activity Relationship; D018243:Teratocarcinoma; D014407:Tumor Cells, Cultured
D002243:Carbolines; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011719:Pyrazines; D011804:Quinolines; C041667:vesnarinone