Effects of choline acetyltransferase inhibitors on the growth and differentiation of mouse neuroblastoma cells in culture.
The effect of cholineacetyltransferase (ChA) inhibitors, bromoacetylcholine (BrACh), 2-benzoylethyltrimethylammonium (BETA), 3-benzoylpropyltrimethylammonium (BPTA), BETA's tertiary analog (TA-BETA) and 4-oxopentyltrimethylammonium (OPTA), on the growth of two types of neuroblastoma (NB) clones, NBE- and NBP2, were studied for the criteria of growth inhibition. Growth inhibitory activities of these agents for the NBE- cells were in the order of: BrACh (ED50: 1 microM) greater than BETA (3.8 microM) greater than BPTA (5.2 microM) greater than TA-BETA (6.5 microM) greater than OPTA (greater than 10 microM). Their potency for growth inhibition in NBP2 clone reflected the order of: BrACh (ED50: 2 microM) greater than BETA (7.8 microM) congruent to BPTA congruent to (greater than 10 microM) congruent to TA-BETA congruent to OPTA. Morphologic differentiation in NBP2 clone was observed with BETA (ED50=9 microM) and its tertiary analog. These results indicate that the NBE- clone is more sensitive to ChA inhibitors for the criteria of growth inhibition than NBP2, and BETA is a potent inducer of morphological differentiation. The fact that some of the inhibitors of ChA inhibit the growth at micromolar concentrations suggests that they may be potentially useful anticancer agents for NB tumors.
D000109:Acetylcholine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000037:antagonists & inhibitors*; D051379:Mice; D009374:Neoplasms, Experimental / Q000473:pathology; D009447:Neuroblastoma / Q000188:drug therapy / Q000473:pathology*
C017058:(2-benzoylethyl)trimethylammonium; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine