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The synthetic oleanane triterpenoid CDDO-Me binds and inhibits pyruvate kinase M2

Iaci N Soares1, Raiane Viana2, Charles B Trelford1

  • 1Department of Physiology and Pharmacology, University of Western Ontario, London, ON, N6A 5C1, Canada.

Pharmacological Reports : PR
|February 11, 2020
PubMed
Abstract

Insights

Synthetic triterpenoid derivatives CDDO-Me and CDDO-Im inhibit lung tumor cell migration by targeting pyruvate kinase M2 (PKM2). These compounds reduce PKM2 activity, suggesting a therapeutic strategy for cancers reliant on this metabolic enzyme.

Area of Science:

  • Biochemistry
  • Cancer Biology
  • Pharmacology

Background:

  • Pyruvate kinase M2 (PKM2) drives the Warburg effect and cancer cell metabolism.
  • Elevated PKM2 is common in tumors, making it a therapeutic target.

Purpose of the Study:

  • To investigate the effect of synthetic oleanane triterpenoid derivatives (CDDO-Me, CDDO-Im) on lung tumor cell migration.
  • To determine if PKM2 is a direct target of these compounds.

Main Methods:

  • Scratch and transwell assays to monitor cell migration.
  • Pull-down and activity assays to assess PKM2 binding and inhibition.
  • Subcellular fractionation and immunofluorescence microscopy for PKM2 localization.
  • PKM2 knockdown cell lines to evaluate migration under varying conditions.

Main Results:

  • CDDO-Me and CDDO-Im significantly inhibited H1299 lung tumor cell migration.
  • CDDO-Me directly bound and reduced the catalytic activity of PKM2.
  • PKM2 knockdown reduced cell migration under glucose/oxygen deprivation, not normal conditions.

Conclusions:

  • PKM2 contributes to tumor cell migration in a tumor-like microenvironment.
  • Synthetic triterpenoid derivatives effectively down-regulate PKM2 activity.
Keywords:
CDDO-MeCancerCell migrationPKM2TriterpenoidWarburg effect

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