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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

p53 Protects lung cancer cells against metabolic stress

Chompunoot Sinthupibulyakit1, Wanida Ittarat, William H St Clair

  • 1Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536, USA.

International Journal of Oncology
|November 3, 2010
PubMed

Insights

The glycolytic inhibitor 2-deoxy-D-glucose (2DG) shows cytotoxicity in non-small cell lung cancer cells. This effect is p53-dependent, with p53-deficient cells being more susceptible to 2DG treatment.

Area of Science:

  • Oncology
  • Cancer Metabolism
  • Molecular Biology

Background:

  • The Warburg effect, preferential aerobic glycolysis in cancer, is a therapeutic target.
  • The efficacy of inhibiting glycolysis across all cancer types remains uncertain.

Purpose of the Study:

  • To investigate the cytotoxic effect of the glycolytic inhibitor 2-deoxy-D-glucose (2DG) on non-small cell lung cancer (NSCLC).
  • To determine the role of p53 in mediating the response to 2DG in NSCLC.

Main Methods:

  • Treatment of p53-deficient (H358) and p53-wild-type (A549) NSCLC cells with 2DG.
  • Assessment of ATP production and oxidative phosphorylation (OXPHOS) capacity.
  • Analysis of reactive oxygen species (ROS) levels and expression of p53 target genes and antioxidant enzymes.

Main Results:

  • 2DG significantly inhibited ATP production in p53-deficient cells but not in p53-wild-type cells.
  • p53-wild-type cells compensated for inhibited glycolysis via OXPHOS, unlike p53-deficient cells.
  • p53-dependent induction of antioxidant enzymes (MnSOD, GPx1) and metabolic regulators (SCO2, TIGAR) was observed.

Conclusions:

  • The cytotoxic effect of 2DG is more efficient in cancer cells lacking functional p53.
  • p53 protects cancer cells against metabolic stress induced by glycolytic inhibition through enhanced OXPHOS and antioxidant defense.

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