PARP Inhibition by Flavonoids Induced Selective Cell Killing to BRCA2-Deficient Cells
1
Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA
2
Research and Development Group, Toyo Sugar Refining Co., Ltd., Tokyo 103-0046, Japan
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2017, 10(4), 80; https://doi.org/10.3390/ph10040080
Received: 5 September 2017 / Revised: 26 September 2017 / Accepted: 6 October 2017 / Published: 12 October 2017
High consumption of dietary flavonoids might contribute to a reduction of cancer risks. Quercetin and its glycosides have PARP inhibitory effects and can induce selective cytotoxicity in BRCA2-deficient cells by synthetic lethality. We hypothesized that common flavonoids in diet naringenin, hesperetin and their glycosides have a similar structure to quercetin, which might have comparable PARP inhibitory effects, and can induce selective cytotoxicity in BRCA2-deficient cells. We utilized Chinese hamster V79 wild type, V-C8 BRCA2-deficient and its gene-complemented cells. In vitro analysis revealed that both naringenin and hesperetin present a PARP inhibitory effect. This inhibitory effect is less specific than for quercetin. Hesperetin was more cytotoxic to V79 cells than quercetin and naringenin based on colony formation assay. Quercetin and naringenin killed V-C8 cells with lower concentrations, and presented selective cytotoxicity to BRCA2-deficient cells. However, the cytotoxicity of hesperetin was similar among all three cell lines. Glycosyl flavonoids, isoquercetin and rutin as well as naringin showed selective cytotoxicity to BRCA2-deficient cells; hesperidin did not. These results suggest that flavonoids with the PARP inhibitory effect can cause synthetic lethality to BRCA2-deficient cells when other pathways are not the primary cause of death.
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Keywords:
quercetin; naringenin; hesperetin; PARP; BRCA2
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MDPI and ACS Style
Su, C.; Haskins, A.H.; Omata, C.; Aizawa, Y.; Kato, T.A. PARP Inhibition by Flavonoids Induced Selective Cell Killing to BRCA2-Deficient Cells. Pharmaceuticals 2017, 10, 80.
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