Related Experiment Video

Updated: Jun 18, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Troglitazone reverses the multiple drug resistance phenotype in cancer cells

Gerald F Davies1, Bernhard H J Juurlink, Troy A A Harkness

  • 1Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, Canada.

Drug Design, Development and Therapy
|November 19, 2009
PubMed

Insights

Troglitazone (TRG) re-sensitizes drug-resistant cancer cells, including breast and leukemia, to doxorubicin (DOX) by reducing key drug resistance proteins. This suggests TRG as a potential adjunct therapy for chemoresistant cancers.

Area of Science:

  • Oncology
  • Pharmacology
  • Epigenetics

Background:

  • Cancer drug resistance, particularly to doxorubicin (DOX), is a major clinical challenge.
  • Previous studies linked DOX resistance in K562 leukemia cells to increased glyoxalase 1 (GLO-1) and histone H3.
  • Troglitazone (TRG) previously reversed DOX resistance by modulating GLO-1 and histone H3.

Purpose of the Study:

  • To investigate if TRG can overcome the multidrug resistance (MDR) phenotype in various cancer cell lines.
  • To determine the role of TRG in downregulating key drug efflux pumps associated with MDR.

Main Methods:

  • Established DOX-resistant cell lines (K562/DOX and MCF7/DOX) from human leukemia and breast cancer cells.
  • Utilized Western blot to analyze expression of P-glycoprotein (MDR-1) and breast cancer resistance protein (BCRP).
  • Assessed the effect of TRG and peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor GW9662 on drug sensitivity and protein expression.

Main Results:

  • TRG significantly decreased the expression of MDR-1 and BCRP in resistant K562/DOX and MCF7/DOX cells.
  • TRG treatment restored sensitivity to DOX in these resistant cancer cell lines.
  • Silencing MDR-1 also sensitized MCF7/DOX cells to DOX, confirming MDR-1's role.
  • TRG's effects were independent of PPARγ, though PPARγ appears involved in MDR and antagonized by TRG.

Conclusions:

  • TRG effectively downregulates MDR-1 and BCRP, restoring sensitivity to doxorubicin in resistant cancer cells.
  • The mechanism of TRG's action on MDR is independent of PPARγ.
  • TRG shows promise as an adjunctive therapy to overcome chemoresistance in various cancers.
Keywords:
breast cancer resistance protein-1chemotherapydoxorubicinmultiple drug resistancemultiple drug resistance protein 1

More Related Videos

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

Related Concept Videos

Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood glucose levels...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a significant...
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
Oral Hypoglycemic Agents: Glinides01:06

Oral Hypoglycemic Agents: Glinides

Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively manages...
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...