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Article

The Effect of Green and Black Tea Polyphenols on BRCA2 Deficient Chinese Hamster Cells by Synthetic Lethality through PARP Inhibition

1
Department of Environmental & Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA
2
Cell Molecular Biology Program, Colorado State University, Fort Collins, CO 80523, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(6), 1274; https://doi.org/10.3390/ijms20061274
Received: 25 February 2019 / Revised: 7 March 2019 / Accepted: 9 March 2019 / Published: 14 March 2019
(This article belongs to the Special Issue Polyphenols: Nutrition, Physiology, Metabolism and Health Benefits)
Tea polyphenols are known antioxidants presenting health benefits due to their observed cellular activities. In this study, two tea polyphenols, epigallocatechin gallate, which is common in green tea, and theaflavin, which is common in black tea, were investigated for their PARP inhibitory activity and selective cytotoxicity to BRCA2 mutated cells. The observed cytotoxicity of these polyphenols to BRCA2 deficient cells is believed to be a result of PARP inhibition induced synthetic lethality. Chinese hamster V79 cells and their BRCA2 deficient mutant V-C8, and V-C8 with gene complemented cells were tested against epigallocatechin gallate and theaflavin. In addition, Chinese hamster ovary (CHO) wild-type cells and rad51D mutant 51D1 cells were used to further investigate the synthetic lethality of these molecules. The suspected PARP inhibitory activity of epigallocatechin and theaflavin was confirmed through in vitro and in vivo experiments. Epigallocatechin gallate showed a two-fold increase of cytotoxicity to V-C8 cells compared to V79 and gene complimented cells. Compared to CHO wild type cells, 51D1 cells also showed elevated cytotoxicity following treatment with epigallocatechin gallate. Theaflavin, however, showed a similar increase of cytotoxicity to VC8 compared to V79 and gene corrected cells, but did not show elevation of cytotoxicity towards rad51D mutant cells compared to CHO cells. Elevation of sister chromatid exchange formation was observed in both tea polyphenol treatments. Polyphenol treatment induced more micronuclei formation in BRCA2 deficient cells and rad51D deficient cells when compared against the respective wild type cells. In conclusion, tea polyphenols, epigallocatechin gallate, and theaflavin may present selective cytotoxicity to BRCA2 deficient cells through synthetic lethality induced by PARP inhibition. View Full-Text
Keywords: theaflavin; epigallocatechin gallate; PARP; BRCA2; synthetic lethality theaflavin; epigallocatechin gallate; PARP; BRCA2; synthetic lethality
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MDPI and ACS Style

Alqahtani, S.; Welton, K.; Gius, J.P.; Elmegerhi, S.; Kato, T.A. The Effect of Green and Black Tea Polyphenols on BRCA2 Deficient Chinese Hamster Cells by Synthetic Lethality through PARP Inhibition. Int. J. Mol. Sci. 2019, 20, 1274. https://doi.org/10.3390/ijms20061274

AMA Style

Alqahtani S, Welton K, Gius JP, Elmegerhi S, Kato TA. The Effect of Green and Black Tea Polyphenols on BRCA2 Deficient Chinese Hamster Cells by Synthetic Lethality through PARP Inhibition. International Journal of Molecular Sciences. 2019; 20(6):1274. https://doi.org/10.3390/ijms20061274

Chicago/Turabian Style

Alqahtani, Shaherah, Kelly Welton, Jeffrey P. Gius, Suad Elmegerhi, and Takamitsu A. Kato 2019. "The Effect of Green and Black Tea Polyphenols on BRCA2 Deficient Chinese Hamster Cells by Synthetic Lethality through PARP Inhibition" International Journal of Molecular Sciences 20, no. 6: 1274. https://doi.org/10.3390/ijms20061274

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