Glycolytic cancer cells lacking 6-phosphogluconate dehydrogenase metabolize glucose to induce senescence

FEBS Lett. 2012 Jul 30;586(16):2389-95. doi: 10.1016/j.febslet.2012.05.052. Epub 2012 Jun 4.

Abstract

We show that knockdown of 6-phosphogluconate dehydrogenase (6PGD) of the pentose phosphate pathway (PPP) inhibits growth of lung cancer cells by senescence induction. This inhibition is not due to a defect in the oxidative PPP per se. NADPH and ribose phosphate production are normal in 6PGD knockdown cells and shutdown of PPP by knockdown of glucose-6-phosphate dehydrogenase (G6PD) has little effect on cell growth. Moreover, 6PGD knockdown cells can proliferate when the PPP is bypassed by using fructose instead of glucose in medium. Significantly, G6PD knockdown rescues proliferation of cells lacking 6PGD, suggesting an accumulation of growth inhibitory glucose metabolics in cells lacking 6PGD. Therefore, 6PGD inhibition may provide a novel strategy to treat glycolyic tumors such as lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Cellular Senescence
  • Gene Expression Regulation, Neoplastic*
  • Glucose / metabolism*
  • Glycolysis
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Mice
  • Mice, Nude
  • Oxidative Stress
  • Oxygen / chemistry
  • Oxygen Consumption
  • Pentose Phosphate Pathway
  • Phosphogluconate Dehydrogenase / genetics*
  • Phosphogluconate Dehydrogenase / metabolism
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Tumor Suppressor Protein p53
  • Phosphogluconate Dehydrogenase
  • Glucose
  • Oxygen