Type

Journal Article

Authors

M Clynes
Y Liang
R O'Connor
V G Martinez

Subjects

Microbiology

Topics
humans pharmacology metabolism gene expression drug resistance docetaxel antineoplastic agents enzyme induction taxoids genetics drug effects drug therapy cell line tumor breast neoplasms cell survival aryl hydrocarbon hydroxylases cytochrome p450 organ specificity family 1 rna small interfering polypeptide 1

CYP1B1 expression is induced by docetaxel: effect on cell viability and drug resistance. (2008)

Abstract The cytochrome P450 CYP1B1 is consistently overexpressed in tumour cells as compared to their normal counterparts, but its precise role in drug resistance is yet to be defined. It has been reported that transfection of CYP1B1 results in increased resistance to docetaxel in V79 cells (McFadyen et al, 2001). In this study, we analysed changes in expression of CYP1B1 mRNA associated with pulse selection of MCF-7 cells with docetaxel. Docetaxel-selected MCF-7 cells (MCF-7 Txt), which showed increased resistance to this drug as compared to parental MCF-7 cells, showed a noteworthy increase in CYP1B1 mRNA expression, paralleled by increased ethoxyresorufin-O-deethylase (EROD) activity levels. This effect was not observed in cisplatin- or adriamycin-selected MCF-7 cells, or in docetaxel-selected colon, lung or pancreatic carcinoma cells. Short-term treatment with docetaxel induced CYP1B1 mRNA expression in MDA 453 and BT-20 breast carcinoma cells, but not in MCF-7 cells. Transfection of MCF-7 Txt cells with CYP1B1 siRNA did not significantly affect docetaxel-induced toxicity, but it decreased cell survival in the absence of drug. Preincubation of docetaxel with recombinant CYP1B1 did not affect drug toxicity in A549 cells. These results suggest that CYP1B1 does not directly inactivate docetaxel, but rather might promote cell survival in MCF-7 Txt cells, providing an explanation for its association with drug resistance.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

M Clynes, Y Liang, R O'Connor, V G Martinez

Experts in our system

1
Martin Clynes
Dublin City University
Total Publications: 209
 
2
Robert O'Connor
Dublin City University
Total Publications: 71