Thioridazine induces apoptosis of multidrug-resistant mouse lymphoma cells transfected with the human ABCB1 and inhibits the expression of P-glycoprotein

Gabriella Spengler, Joseph Molnar, Miguel Viveiros, Leonard Amaral

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

AIM: 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.

MATERIALS AND 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.

CONCLUSION: 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.

Original languageEnglish
Pages (from-to)4201-4205
Number of pages5
JournalAnticancer Research
Volume31
Issue number12
Publication statusPublished - Dec 2011

Keywords

  • Animals
  • Apoptosis
  • Biological Transport
  • Cell Line, Tumor
  • Chemotherapy, Adjuvant
  • Dopamine Antagonists
  • Drug Resistance, Multiple
  • Drug Synergism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphoma
  • Mice
  • P-Glycoprotein
  • P-Glycoproteins
  • Thioridazine
  • Transfection
  • Journal Article
  • Research Support, Non-U.S. Gov't

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