Effect of thioridazine stereoisomers on the drug accumulation of mouse lymphoma and human prostate cancer cell lines in vitro

Ákos Csonka, Gabriella Spengler, Ana Martins, Imre Ocsovszki, Jørn B. Christensen, Oliver Hendricks, Jette E. Kristiansen, Leonard Amaral, Joseph Molnar

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Cancer cells become refractory to chemotherapy as a consequence of their overexpression of multidrug transporters. Materials and 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 overexpressing 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-iphenyl 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. Conclusion: Apparently, the chirality of thioridazine has no importance in the inhibition of MDR phenotype of cancer cells.

Original languageEnglish
Pages (from-to)815-820
Number of pages6
JournalIn Vivo
Volume27
Issue number6
Publication statusPublished - Nov 1 2013

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Keywords

  • ABCB1 transporter
  • Apoptosis induction
  • Enantiomers
  • Mouse lymphoma
  • Multidrug resistance
  • PC3 prostate cancer cell line
  • Thioridazine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology

Cite this

Csonka, Á., Spengler, G., Martins, A., Ocsovszki, I., Christensen, J. B., Hendricks, O., Kristiansen, J. E., Amaral, L., & Molnar, J. (2013). Effect of thioridazine stereoisomers on the drug accumulation of mouse lymphoma and human prostate cancer cell lines in vitro. In Vivo, 27(6), 815-820.