Related Experiment Video

Updated: May 31, 2026

Oxygen-Independent Assays to Measure Mitochondrial Function in Mammals
05:59

Oxygen-Independent Assays to Measure Mitochondrial Function in Mammals

Published on: May 19, 2023

Modulation of doxorubicin resistance by the glucose-6-phosphate dehydrogenase activity

Manuela Polimeni1, Claudia Voena, Joanna Kopecka

  • 1Department of Genetics, Biology and Biochemistry, University of Torino, Via Santena 5/bis, 10126 Torino, Italy. manuela.polimeni@unito.it

The Biochemical Journal
|June 18, 2011
PubMed

Insights

Increased glucose-6-phosphate dehydrogenase (G6PD) activity boosts glutathione (GSH) levels, enhancing cancer cell resistance to chemotherapy drugs by activating efflux pumps. Inhibiting G6PD reverses this multidrug resistance (MDR).

Area of Science:

  • Biochemistry
  • Cancer Biology
  • Pharmacology

Background:

  • Multidrug resistance (MDR) in cancer is a significant clinical challenge.
  • The precise mechanisms by which anti-neoplastic agents induce MDR and the role of glutathione (GSH) in pump activation remain incompletely understood.
  • MDR-associated proteins (MRPs) are implicated in drug efflux.

Purpose of the Study:

  • To investigate the role of the pentose phosphate pathway (PPP) and glucose-6-phosphate dehydrogenase (G6PD) in the development of doxorubicin resistance in human colon cancer cells.
  • To elucidate the relationship between G6PD activity, intracellular GSH levels, and MDR.
  • To explore the potential of G6PD inhibitors in overcoming MDR.

Main Methods:

  • Comparison of doxorubicin-sensitive (HT29) and doxorubicin-resistant (HT29-DX) human colon cancer cell lines.
  • Measurement of doxorubicin accumulation, intracellular GSH content, MRP1 and MRP2 expression.
  • Assay of pentose phosphate pathway (PPP) activity and glucose-6-phosphate dehydrogenase (G6PD) activity.
  • Treatment with G6PD inhibitors dehydroepiandrosterone (DHEA) and 6-aminonicotinamide (6-AN).

Main Results:

  • Doxorubicin-resistant HT29-DX cells exhibited decreased doxorubicin accumulation, increased intracellular GSH, and elevated MRP1/MRP2 expression compared to sensitive HT29 cells.
  • HT29 cells overexpressing G6PD showed increased MDR and elevated GSH levels.
  • G6PD inhibitors (DHEA, 6-AN) reduced G6PD and GSH levels and inhibited MDR in both HT29-DX and G6PD-overexpressing HT29 cells.

Conclusions:

  • Activation of the PPP and increased G6PD activity are crucial for maintaining high GSH levels in certain MDR cancer cells.
  • Elevated GSH is necessary for the extrusion of anticancer drugs, contributing to MDR acquisition.
  • These findings suggest a novel mechanism linking G6PD, GSH, and MDR, offering potential therapeutic targets.

More Related Videos

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration11:13

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration

Published on: June 9, 2023

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen19:44

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

Related Concept Videos

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...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...