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

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...

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Autores principales: Alqahtani, Shaherah, Welton, Kelly, Gius, Jeffrey P., Elmegerhi, Suad, Kato, Takamitsu A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470602/
https://www.ncbi.nlm.nih.gov/pubmed/30875717
http://dx.doi.org/10.3390/ijms20061274
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author Alqahtani, Shaherah
Welton, Kelly
Gius, Jeffrey P.
Elmegerhi, Suad
Kato, Takamitsu A.
author_facet Alqahtani, Shaherah
Welton, Kelly
Gius, Jeffrey P.
Elmegerhi, Suad
Kato, Takamitsu A.
author_sort Alqahtani, Shaherah
collection PubMed
description 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.
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spelling pubmed-64706022019-04-26 The Effect of Green and Black Tea Polyphenols on BRCA2 Deficient Chinese Hamster Cells by Synthetic Lethality through PARP Inhibition Alqahtani, Shaherah Welton, Kelly Gius, Jeffrey P. Elmegerhi, Suad Kato, Takamitsu A. Int J Mol Sci Article 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. MDPI 2019-03-14 /pmc/articles/PMC6470602/ /pubmed/30875717 http://dx.doi.org/10.3390/ijms20061274 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Alqahtani, Shaherah
Welton, Kelly
Gius, Jeffrey P.
Elmegerhi, Suad
Kato, Takamitsu A.
The Effect of Green and Black Tea Polyphenols on BRCA2 Deficient Chinese Hamster Cells by Synthetic Lethality through PARP Inhibition
title The Effect of Green and Black Tea Polyphenols on BRCA2 Deficient Chinese Hamster Cells by Synthetic Lethality through PARP Inhibition
title_full The Effect of Green and Black Tea Polyphenols on BRCA2 Deficient Chinese Hamster Cells by Synthetic Lethality through PARP Inhibition
title_fullStr The Effect of Green and Black Tea Polyphenols on BRCA2 Deficient Chinese Hamster Cells by Synthetic Lethality through PARP Inhibition
title_full_unstemmed The Effect of Green and Black Tea Polyphenols on BRCA2 Deficient Chinese Hamster Cells by Synthetic Lethality through PARP Inhibition
title_short The Effect of Green and Black Tea Polyphenols on BRCA2 Deficient Chinese Hamster Cells by Synthetic Lethality through PARP Inhibition
title_sort effect of green and black tea polyphenols on brca2 deficient chinese hamster cells by synthetic lethality through parp inhibition
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470602/
https://www.ncbi.nlm.nih.gov/pubmed/30875717
http://dx.doi.org/10.3390/ijms20061274
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