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Updated: Jan 21, 2026

Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes
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Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes

Published on: June 25, 2017

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Reduced chemotherapeutic sensitivity in high glucose condition: implication of antioxidant response

Alessia Garufi1,2, Gianandrea Traversi1,2, Maria Saveria Gilardini Montani3

  • 1IRCCS Regina Elena National Cancer Institute, Department of Research, Rome 00144, Italy.

Oncotarget
|August 7, 2019
PubMed

Insights

High glucose levels reduce chemotherapy effectiveness by decreasing reactive oxygen species (ROS) and increasing antioxidant NRF2 activity. Inhibiting NRF2 restores cancer cell sensitivity to Adriamycin (ADR).

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Chemotherapy resistance is a significant challenge in cancer treatment.
  • Reactive oxygen species (ROS) mediate the cytotoxic effects of anticancer drugs like Adriamycin (ADR).
  • Altered oxidative balance is linked to chemotherapy resistance.

Purpose of the Study:

  • To investigate the mechanism by which high glucose (HG) impairs the cytotoxic effect of ADR.
  • To elucidate the role of the NRF2 pathway in HG-induced chemoresistance.

Main Methods:

  • Colon cancer cells were treated with ADR under high glucose conditions.
  • Measured ADR-induced ROS production, H2AX phosphorylation, and micronuclei (MN) formation.
  • Assessed the impact of NRF2 pathway inhibition using brusatol.

Main Results:

  • HG significantly attenuated ADR-induced ROS production in colon cancer cells.
  • This attenuation led to reduced ADR-induced H2AX phosphorylation and MN formation.
  • HG-mediated reduction in ROS correlated with enhanced NRF2 activity and antioxidant response.
  • Pharmacological inhibition of NRF2 with brusatol restored ADR's cytotoxic effect in HG.

Conclusions:

  • High glucose conditions promote chemoresistance by upregulating the NRF2-mediated antioxidant response.
  • Inhibition of the NRF2 pathway can overcome HG-induced resistance to ADR.
  • These findings offer insights into restoring chemosensitivity in high glucose environments.
Keywords:
cancerchemoresistancehigh glucose (HG)nuclear factor erythroid 2-related factor 2 (NRF2)reactive oxygen species (ROS)

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