Similar pyruvate kinase modifications in glioblastoma cells by 7β-hydroxycholesterol and glutamine withdrawal

Biochem Pharmacol. 2013 Jul 1;86(1):161-7. doi: 10.1016/j.bcp.2013.03.012. Epub 2013 Mar 26.

Abstract

Oxysterols possess anti-proliferative properties that may be used with much effect in the treatment of cancer. We have demonstrated previously that 7 beta-hydroxycholesterol (7b-HC) provokes both metabolic stress, as witnessed by AMPK activation, and changes in lipid raft composition in C6 glioblastoma cells. These observations suggested that glycolysis might have been changed. Here we will show that 7b-HC increases cell cycle time and that it changes the affinity of pyruvate kinase to its substrate, phosphoenol pyruvate. The latter effect is mimicked by glutamine withdrawal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin D1 / metabolism
  • Cyclin E / metabolism
  • Enzyme Activation
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Glutamine / metabolism*
  • Glycolysis
  • Hydroxycholesterols / metabolism*
  • Hydroxycholesterols / pharmacology
  • Phosphoenolpyruvate / metabolism
  • Pyruvate Kinase / metabolism
  • Rats
  • Stress, Physiological

Substances

  • Cyclin E
  • Hydroxycholesterols
  • Glutamine
  • Cyclin D1
  • cholest-5-en-3 beta,7 alpha-diol
  • Phosphoenolpyruvate
  • Pyruvate Kinase
  • AMP-Activated Protein Kinases