title: Effect of thioridazine stereoisomers on the drug accumulation of mouse lymphoma and human prostate cancer cell lines in vitro.
abstract: BACKGROUND
  Cancer cells become refractory to chemotherapy as a consequence of their overexpression of multidrug transporters.
  
  
  METHODS
  The anticancer and multidrug resistance (MDR) reversal effects of the racemic form and the two enantiomers of thoridazine were investigated on a mouse T-lymphoma cell line over-expressing the ATP-binding cassette, subfamily-B (MDR/TAP), member 1 (ABCB1) transporter (also known as P-glycoprotein) and on human PC3 prostate cancer cell line by 3-(4.5-dimethylthiazolyl-2)-2.5-diphenyl tetrazolium bromide (MTT) assay. The modulation of ABCB1 transporter activity was studied by rhodamine123 accumulation, the apoptosis-inducing effect was investigated using fluorescein isothiocyanate (FITC)-labeled annexin V and propidium iodide.
  
  
  RESULTS
  The thioridazine racemic and (+) and (-) enantiomers were similarly effective. Drug accumulation by MDR mouse T-lymphoma cells was moderately modified in the presence of thioridazine derivatives. Thioridazine induced apoptosis of the MDR cancer cell line, but there was no significant apoptotic effect on the PC3 cell line.
  
  
  CONCLUSIONS
  Apparently, the chirality of thioridazine has no importance in the inhibition of MDR phenotype of cancer cells.
authors.affiliation: D.Sc., Institute of Medical Microbiology and Immunobiology, University of Szeged; H-6720 Szeged, Hungary. molnar.jozsef@med.u-szeged.hu.
authors.forename: Ákos
authors.initials: Á
authors.lastname: Csonka
authors.forename: Gabriella
authors.initials: G
authors.lastname: Spengler
authors.forename: Ana
authors.initials: A
authors.lastname: Martins
authors.forename: Imre
authors.initials: I
authors.lastname: Ocsovszki
authors.forename: Jørn B
authors.initials: JB
authors.lastname: Christensen
authors.forename: Oliver
authors.initials: O
authors.lastname: Hendricks
authors.forename: Jette E
authors.initials: JE
authors.lastname: Kristiansen
authors.forename: Leonard
authors.initials: L
authors.lastname: Amaral
authors.forename: Joseph
authors.initials: J
authors.lastname: Molnar
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008223:Lymphoma; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms; D020112:Rhodamine 123 / Q000378:metabolism; D013237:Stereoisomerism; D013881:Thioridazine / Q000494:pharmacology*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D020112:Rhodamine 123; D013881:Thioridazine
keywords: ABCB1 transporter; PC3 prostate cancer cell line; Thioridazine; apoptosis induction; enantiomers; mouse lymphoma; multidrug resistance