Trifluoperazine inhibits spreading and migration of cells in culture.
Trifluoperazine (TFP) blocks spreading and migration of cultured mammalian cells. These are calcium-dependent and microfilament-mediated processes. Calmodulin, a regulator of many calcium-dependent processes in cells, is selectively inhibited by TFP. Cell spreading on a plastic- or collagen-coated substratum was reversibly inhibited by 10 micro M TFP. The drug blocks cell spreading even in the presence of 1 mM cAMP. TFP is as effective as cytochalasin B (CB), in inhibitor of microfilament function, in blocking cell spreading. All cell lines tested, whether "normal" or virally transformed, failed to spread to TFP. The drug, at a concentration sufficient to inhibit spreading, does not interfere with the initial attachment of a cell to a plastic surface. Cells plated in the presence of 10 micro M TFP attach at a rate and to an extent equal to untreated controls. TFP added to already spread cells results in a reversible cell rounding. Detection of fibronectin by indirect immunofluorescence suggests TFP-induced cell rounding is not due to shedding of fibronectin from the cell surface. TFP reversibly blocks cell migration into a would edge almost as effectively as CB. We suggest that TFP interferes with these microfilament-mediated functions by direct action on the microfilaments or indirect action by inactivating calmodulin.
D000818:Animals; D002118:Calcium / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002448:Cell Adhesion / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured / Q000187:drug effects; D002746:Chlorpromazine / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism; D008560:Membrane Fluidity / Q000187:drug effects; D009020:Morphine / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D051381:Rats; D014268:Trifluoperazine / Q000494:pharmacology*
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D005353:Fibronectins; D010868:Pimozide; D014268:Trifluoperazine; D009020:Morphine; D002118:Calcium; D002746:Chlorpromazine