Troglitazone reverses the multiple drug resistance phenotype in cancer cells.

Drug Design, Development and Therapy
Gerald F DaviesT A A Harkness

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...Continue Reading

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May 15, 2013·European Journal of Pharmacology·Yidong FengWenlong Huang
Aug 25, 2012·PPAR Research·Anthony J Apostoli, Christopher J B Nicol
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Feb 3, 2018·International Journal of Molecular Medicine·Jun ChenJianping Xiong
Apr 20, 2021·Frontiers in Oncology·Alessia LeoneClaudia Miele

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Methods Mentioned

BETA
electrophoresis
transfection
fluorescence
acetylation
histone acetylation

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