Induction of apoptosis by Phenothiazine derivatives in V79 cells

Phenothiazine derivatives chlorpromazine (cpz) and trifluoperazine (tfp) we re found to induce apoptosis, abnormal cell cycle and expression of p53 in Chinese hamster lung fibroblast V79 cells. Both the drugs can induce apopto sis when cells are treated with drug at a concentration of 10 mug/ml within 4 h, as detected by propidium. iodide staining and DNA fragmentation analy sis, Flow cytometric analysis revealed that the apoptotic response is media ted by a loss of Gt population of cells. In Western blot analysis, p21 is i nduced and p53 is accompanied by additional bands. Also indirect immunolabe ling of single cells revealed that p21 is accumulated from cytoplasm into n ucleus after the drug treatment and the intensities of p53 increased. Our f indings demonstrate for the first time that phenothiazine derivatives, in a ddition to their cytotoxic effects, could induce apoptosis, an observation that has important clinical implications. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.