Tranquillizers can block mitogenesis in 3T3 cells and induce differentiation in Friend cells.
Compounds of diverse structure induce murine Friend erythroleukaemia (MEL) cell differentiation. Seeking a common property, Bernstein reported that the relationship between activity and octanol/water partition coefficients for inducers resembled that reported for anaesthetics; moreover, anaesthetics inhibited induction. Since anaesthetics were known to increase membrane fluidity, they suggested that inducers might decrease it. Reporting evidence against unitary theories of anaesthesia, Richards et al. suggested that lipophilic drugs competed, according to their individual structure, with membrane lipids for hydrophobic regions on membrane proteins. The antagonism between pairs of anaesthetics, anaesthetics and inducers and pairs of inducers, might thus be explained economically by Richards' anaesthesia model, inducers and lipophilic drugs acting by similar rather than contrary mechanisms. Lipophilic drugs should, therefore, induce differentiation. We report here that some tranquillizers do so. As reported elsewhere for classical inducers, they also block non-differentiating 3T3 cells in pre-S. These findings may have application in cancer chemotherapy.
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured / Q000187:drug effects; D005622:Friend murine leukemia virus; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D008563:Membrane Lipids; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D009374:Neoplasms, Experimental / Q000473:pathology; D012995:Solubility; D013329:Structure-Activity Relationship
D008563:Membrane Lipids; D001569:Benzodiazepines