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

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.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Maeda J,Roybal EJ,Brents CA,Uesaka M,Aizawa Y,Kato TA

doi

10.3892/or.2013.2902

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

551-6

issue

2

eissn

1021-335X

issn

1791-2431

journal_volume

31

pub_type

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