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

  • Authors:
    • Junko Maeda
    • Erica J. Roybal
    • Colleen A. Brents
    • Mitsuru Uesaka
    • Yasushi Aizawa
    • Takamitsu A. Kato
  • View Affiliations / Copyright

    Affiliations: Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA, Graduate School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan, Research and Development Group, Toyo Sugar Refining Co., Ltd., Tokyo 103-0046, Japan
    Copyright: © Maeda et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 551-556
    |
    Published online on: December 5, 2013
       https://doi.org/10.3892/or.2013.2902
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Abstract

Poly(ADP-ribose) polymerase (PARP) inhibitors have been proven to represent superior clinical agents targeting DNA repair mechanisms in cancer therapy. We investigated PARP inhibitory effects of the natural and synthetic flavonoids (quercetin, rutin, monoglucosyl rutin and maltooligosyl rutin) and tested the synthetic lethality in BRCA2 mutated cells. In vitro ELISA assay suggested that the flavonoids have inhibitory effects on PARP activity, but glucosyl modifications reduced the inhibitory effect. Cytotoxicity tests of Chinese hamster cells defective in BRCA2 gene (V-C8) and its parental V79 cells showed BRCA2-dependent synthetic lethality when treated with the flavonoids. BRCA2 mutated cells were three times more sensitive to the flavonoids than the wild-type and gene complemented cells. Reduced toxicity was observed in a glucosyl modification-dependent manner. The present study provides support for the clinical use of new treatment drugs, and is the beginning of the potential application of flavonoids in cancer prevention and the periodic consumption of appropriate flavonoids to reduce cancer risk in individuals carrying a mutant allele of the BRCA2 gene.
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Copy and paste a formatted citation
Spandidos Publications style
Maeda J, Roybal EJ, Brents CA, Uesaka M, Aizawa Y and Kato TA: Natural and glucosyl flavonoids inhibit poly(ADP-ribose) polymerase activity and induce synthetic lethality in BRCA mutant cells. Oncol Rep 31: 551-556, 2014.
APA
Maeda, J., Roybal, E.J., Brents, C.A., Uesaka, M., Aizawa, Y., & Kato, T.A. (2014). Natural and glucosyl flavonoids inhibit poly(ADP-ribose) polymerase activity and induce synthetic lethality in BRCA mutant cells. Oncology Reports, 31, 551-556. https://doi.org/10.3892/or.2013.2902
MLA
Maeda, J., Roybal, E. J., Brents, C. A., Uesaka, M., Aizawa, Y., Kato, T. A."Natural and glucosyl flavonoids inhibit poly(ADP-ribose) polymerase activity and induce synthetic lethality in BRCA mutant cells". Oncology Reports 31.2 (2014): 551-556.
Chicago
Maeda, J., Roybal, E. J., Brents, C. A., Uesaka, M., Aizawa, Y., Kato, T. A."Natural and glucosyl flavonoids inhibit poly(ADP-ribose) polymerase activity and induce synthetic lethality in BRCA mutant cells". Oncology Reports 31, no. 2 (2014): 551-556. https://doi.org/10.3892/or.2013.2902
Copy and paste a formatted citation
x
Spandidos Publications style
Maeda J, Roybal EJ, Brents CA, Uesaka M, Aizawa Y and Kato TA: Natural and glucosyl flavonoids inhibit poly(ADP-ribose) polymerase activity and induce synthetic lethality in BRCA mutant cells. Oncol Rep 31: 551-556, 2014.
APA
Maeda, J., Roybal, E.J., Brents, C.A., Uesaka, M., Aizawa, Y., & Kato, T.A. (2014). Natural and glucosyl flavonoids inhibit poly(ADP-ribose) polymerase activity and induce synthetic lethality in BRCA mutant cells. Oncology Reports, 31, 551-556. https://doi.org/10.3892/or.2013.2902
MLA
Maeda, J., Roybal, E. J., Brents, C. A., Uesaka, M., Aizawa, Y., Kato, T. A."Natural and glucosyl flavonoids inhibit poly(ADP-ribose) polymerase activity and induce synthetic lethality in BRCA mutant cells". Oncology Reports 31.2 (2014): 551-556.
Chicago
Maeda, J., Roybal, E. J., Brents, C. A., Uesaka, M., Aizawa, Y., Kato, T. A."Natural and glucosyl flavonoids inhibit poly(ADP-ribose) polymerase activity and induce synthetic lethality in BRCA mutant cells". Oncology Reports 31, no. 2 (2014): 551-556. https://doi.org/10.3892/or.2013.2902
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