Drug Design, Development and Therapy
Open access peer-reviewed scientific and medical journals.
Dove Medical Press is now a member of the Open Access Initiative
An Author's Guide
A guide to help authors get their paper published.
Support Open Access and Dove Press
Promotional Article Monitoring - further details
Favored Author Program
Real benefits for authors, including fast-track processing of papers.
Troglitazone reverses the multiple drug resistance phenotype in cancer cells
(6702) Total Article Views
Authors: Gerald F Davies, Bernhard HJ Juurlink, Troy AA Harkness
Published Date March 2009
Volume 2009:3 Pages 79 - 88
Gerald F Davies1, Bernhard HJ Juurlink2, Troy AA Harkness1
1Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, Canada; 2College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia
Abstract: A major problem in treating cancer is the development of drug resistance. We previously demonstrated doxorubicin (DOX) resistance in K562 human leukemia cells that was associated with upregulation of glyoxalase 1 (GLO-1) and histone H3 expression. The thiazolidinedione troglitazone (TRG) downregulated GLO-1 expression and further upregulated histone H3 expression and post-translational modifications in these cells, leading to a regained sensitivity to DOX. Given the pleiotropic effects of epigenetic changes in cancer development, we hypothesized that TRG may downregulate the multiple drug resistance (MDR) phenotype in a variety of cancer cells. To test this, MCF7 human breast cancer cells and K562 cells were cultured in the presence of low-dose DOX to establish DOX-resistant cell lines (K562/DOX and MCF7/DOX). The MDR phenotype was confirmed by Western blot analysis of the 170 kDa P-glycoprotein (Pgp) drug efflux pump multiple drug resistance protein 1 (MDR-1), and the breast cancer resistance protein (BCRP). TRG markedly decreased expression of both MDR-1 and BCRP in these cells, resulting in sensitivity to DOX. Silencing of MDR-1 expression also sensitized MCF7/DOX cells to DOX. Use of the specific and irreversible peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor GW9662 in the nanomolar range not only demonstrated that the action of TRG on MCF/DOX was PPARγ-independent, but indicated that PPARγ may play a role in the MDR phenotype, which is antagonized by TRG. We conclude that TRG is potentially a useful adjunct therapy in chemoresistant cancers.
Keywords: chemotherapy, doxorubicin, breast cancer resistance protein-1, multiple drug resistance, multiple drug resistance protein 1
Cannotea Citeulike Del.icio.us Facebook LinkedIn Twitter
Readers of this article also read:
"I was impressed at the rapidity of publication from submission to final acceptance." Dr Edwin Thrower, PhD, Yale University.
- Enzalutamide: an evidence-based review of its use in the treatment of prostate cancer
- The benefits and risks of testosterone replacement therapy: a review
- Tumor necrosis factor-alpha inhibitor treatment for sarcoidosis
- Tenofovir-associated bone density loss