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

• Published in: International journal of molecular sciences Vol. 20; no. 6; p. 1274
• Main Authors: Alqahtani, Shaherah, Welton, Kelly, Gius, Jeffrey P, Elmegerhi, Suad, Kato, Takamitsu A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.03.2019; MDPI
• Subjects: Antioxidants; Black tea; BRCA2; BRCA2 protein; Cell culture; Cell cycle; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA repair; Epigallocatechin gallate; Flavonoids; Homologous recombination; Homology; Ionizing radiation; Mutation; PARP; Poly(ADP-ribose) polymerase; Polyphenols; Proteins; Repair; Statistical analysis; Statistical significance; Survival; synthetic lethality; Tea; theaflavin; PARP; epigallocatechin gallate; BRCA2; theaflavin; synthetic lethality
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20061274

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 mutated cells. The observed cytotoxicity of these polyphenols to deficient cells is believed to be a result of PARP inhibition induced synthetic lethality. Chinese hamster V79 cells and their 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 deficient cells and deficient cells when compared against the respective wild type cells. In conclusion, tea polyphenols, epigallocatechin gallate, and theaflavin may present selective cytotoxicity to deficient cells through synthetic lethality induced by PARP inhibition.