title: Thioridazine induces apoptosis of multidrug-resistant mouse lymphoma cells transfected with the human ABCB1 and inhibits the expression of P-glycoprotein.
abstract: OBJECTIVE
  Chlorpromazine has activity against a large variety of cancer types. However, this phenothiazine produces a plethora of serious side-effects. We have studied thioridazine (TZ), a phenothiazine neuroleptic that is much milder, for activity against multidrug-resistant (MDR) cancer cells, as well as against the overexpressed ABCB1 transporter (P-glycoprotein) that is the cause for the MDR phenotype of these cancer cells.
  
  
  METHODS
  MDR mouse T-lymphoma cells, transfected with the human gene ABCB1 that codes for the transporter ABCB1, were incubated with TZ for various periods of time and examined for evidence of apoptosis. Concentrations of TZ were evaluated for activity against the ABCB1 transporter with the aid of an automated ethidium bromide (EB) method.
  
  
  RESULTS
  TZ induces apoptosis of MDR cancer cell line, as well as inhibits the activity of the overexpressed ABCB1 transporter of these cells.
  
  
  CONCLUSIONS
  Because thioridazine has been in moderately safe use for over 40 years for the therapy of psychosis, it has the potential to serve as an adjuvant with anticancer agents, rendering the a priori MDR cancer cells susceptible to the anticancer agent.
authors.affiliation: Institute of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Spengler
authors.forename: Joseph
authors.initials: J
authors.lastname: Molnar
authors.forename: Miguel
authors.initials: M
authors.lastname: Viveiros
authors.forename: Leonard
authors.initials: L
authors.lastname: Amaral
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001692:Biological Transport; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant / Q000379:methods; D018492:Dopamine Antagonists / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy*; D051379:Mice; D013881:Thioridazine / Q000494:pharmacology*; D014162:Transfection
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018492:Dopamine Antagonists; D013881:Thioridazine