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Metabolic responses induced by DNA damage and poly (ADP-ribose) polymerase (PARP) inhibition in MCF-7 cells

Vijesh J Bhute1, Sean P Palecek1

  • 1Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.

Metabolomics : Official Journal of the Metabolomic Society
|October 20, 2015
PubMed

Insights

Cancer cells activate DNA damage response pathways that alter metabolism. This study reveals how specific DNA damage types trigger distinct metabolic changes, offering new ways to classify DNA damage responses using metabolomics.

Area of Science:

  • Cancer Biology
  • Metabolomics
  • DNA Damage Response

Background:

  • Genomic instability is a hallmark of cancer.
  • Chemotherapy and radiotherapy induce DNA damage, activating DNA damage response (DDR) pathways.
  • DDR pathways significantly impact cellular metabolism, but these effects are not well understood.

Purpose of the Study:

  • To identify metabolic pathways altered by different DNA damaging agents using NMR metabolomics.
  • To investigate the role of poly (ADP-ribose) polymerase (PARP) in methyl methanesulfonate (MMS)-induced DNA damage and its metabolic consequences.
  • To explore the potential of metabolomics in classifying DNA damage responses.

Main Methods:

  • Utilized Nuclear Magnetic Resonance (NMR) metabolomics to analyze metabolic profiles of MCF-7 cells.
  • Administered DNA damaging agents like methyl methanesulfonate (MMS) and zeocin.
  • Investigated the effect of PARP inhibition using veliparib (ABT-888).

Main Results:

  • Identified activation of PARP and significant NAD+ depletion in response to MMS-induced DNA damage.
  • Demonstrated that veliparib (PARP inhibitor) restored NAD+ levels in MMS-treated cells.
  • Observed similar metabolic responses to double-strand breaks induced by MMS/veliparib and zeocin, suggesting metabolomics can classify DNA damage types.

Conclusions:

  • Cancer cell metabolic responses are specific to the type of DNA damage.
  • Metabolomics can be a valuable tool for classifying DNA damage responses.
  • Understanding DDR-associated metabolic alterations is crucial for cancer therapy.
Keywords:
DNA damageMCF-7NMRPARPmetabolomics

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