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

TY - JOUR

T1 - Effect of thioridazine stereoisomers on the drug accumulation of mouse lymphoma and human prostate cancer cell lines in vitro

AU - Csonka, Ákos

AU - Spengler, Gabriella

AU - Martins, Ana

AU - Ocsovszki, Imre

AU - Christensen, Jørn Bolstad

AU - Hendricks, Oliver

AU - Kristiansen, Jette E.

AU - Amaral, Leonard

AU - Molnar, Joseph

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 24292587

SN - 0258-851X

VL - 27

SP - 815

EP - 820

JO - In Vivo

JF - In Vivo

IS - 6

ER -