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.

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 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.

CONCLUSION:

Apparently, the chirality of thioridazine has no importance in the inhibition of MDR phenotype of cancer cells.

• Authors: Ákos Csonka, Gabriella Spengler, Ana Martins, Imre Ocsovszki, Jørn B Christensen, Oliver Hendricks, Jette E Kristiansen, Leonard Amaral, Joseph Molnar
• Journal: In vivo (Athens, Greece) (In Vivo) 2013 Nov-Dec Vol. 27 Issue 6 Pg. 815-20 ISSN: 1791-7549 [Electronic] Greece
• PMID: 24292587 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCB1 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antineoplastic Agents
• Fluorescent Dyes
• Rhodamine 123
• Thioridazine

Topics

• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm (drug effects)
• Drug Screening Assays, Antitumor
• Fluorescent Dyes (metabolism)
• Humans
• Inhibitory Concentration 50
• Lymphoma
• Male
• Mice
• Prostatic Neoplasms
• Rhodamine 123 (metabolism)
• Stereoisomerism
• Thioridazine (pharmacology)