Induction of apoptosis by Phenothiazine derivatives in V79 cells.
Phenothiazine derivatives chlorpromazine (cpz) and trifluoperazine (tfp) were found to induce apoptosis, abnormal cell cycle and expression of p53 in Chinese hamster lung fibroblast V79 cells. Both the drugs can induce apoptosis when cells are treated with drug at a concentration of 10 microg/ml within 4 h, as detected by propidium iodide staining and DNA fragmentation analysis. Flow cytometric analysis revealed that the apoptotic response is mediated by a loss of G(1) population of cells. In Western blot analysis, p21 is induced and p53 is accompanied by additional bands. Also indirect immunolabeling of single cells revealed that p21 is accumulated from cytoplasm into nucleus after the drug treatment and the intensities of p53 increased. Our findings demonstrate for the first time that phenothiazine derivatives, in addition to their cytotoxic effects, could induce apoptosis, an observation that has important clinical implications.
Karmakar
P
P
Department of Biophysics, Molecular Biology & Genetics, 92, A.P.C. Road, 700 009, Calcutta, India. karmakarp@grc.nia.nih.gov
Natarajan
A T
AT
Poddar
R K
RK
Dasgupta
U B
UB
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D002746:Chlorpromazine / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D014268:Trifluoperazine / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D014268:Trifluoperazine; D002118:Calcium; D002746:Chlorpromazine