Natural and glucosyl flavonoids inhibit poly(ADP-ribose) polymerase activity and induce synthetic lethality in BRCA

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Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
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Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

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Junko Maeda1, Erica J Roybal1, Colleen A Brents1

  • 1Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA.

Oncology Reports
|December 10, 2013
PubMed

Insights

Flavonoids inhibit Poly(ADP-ribose) polymerase (PARP) activity, showing synthetic lethality in BRCA2 mutated cancer cells. Glucosyl modifications reduced these effects, suggesting potential for cancer prevention in individuals with BRCA2 mutations.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Poly(ADP-ribose) polymerase (PARP) inhibitors are key in cancer therapy by targeting DNA repair.
  • Flavonoids are natural and synthetic compounds with potential therapeutic applications.

Purpose of the Study:

  • To investigate the Poly(ADP-ribose) polymerase (PARP) inhibitory effects of various flavonoids.
  • To evaluate the synthetic lethality of these flavonoids in BRCA2-mutated cancer cells.

Main Methods:

  • In vitro ELISA assays to measure PARP inhibition.
  • Cytotoxicity tests on Chinese hamster cells with and without BRCA2 gene mutations (V-C8 and V79 cells).

Main Results:

  • Flavonoids demonstrated inhibitory effects on PARP activity, with glucosyl modifications reducing this inhibition.
  • BRCA2-deficient cells exhibited significantly higher sensitivity (threefold) to flavonoids, indicating BRCA2-dependent synthetic lethality.
  • Toxicity was reduced in a manner dependent on glucosyl modification.

Conclusions:

  • Flavonoids show promise as novel cancer treatment agents, particularly for BRCA2-mutated cancers.
  • The study supports the clinical application of flavonoids and suggests their potential role in cancer prevention.
  • Periodic consumption of specific flavonoids may reduce cancer risk in individuals with BRCA2 mutations.

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