Publication: Effects of folate cycle disruption by the green tea polyphenol epigallocatechin-3-gallate
Authors
Navarro Perán, Encarnación María ; Cabezas Herrera, Juan ; Rodríguez López, José Neptuno ; Sánchez del Campo Ferrer, Luis
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Publisher
PERGAMON-ELSEVIER SCIENCE LTD
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DOI
https://doi.org/10.1016/j.biocel.2007.06.005
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info:eu-repo/semantics/article
Description
©<2007>. This is the Accepted manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Accepted version of a Published Work that appeared in final form in The International Journal of Biochemistry & Cell Biology. To access the final edited and published work see https://doi.org/10.1016/j.biocel.2007.06.005
Abstract
We demonstrate that the tea polyphenol, epigallocatechin-3-gallate, is an efficient inhibitor of human dihydrofolate reductase. Like other antifolate compounds, epigallocatechin-3-gallate acts by disturbing folic acid metabolism in cells, causing the inhibition of DNA and RNA synthesis and altering DNA methylation. Epigallocatechin-3-gallate was seen to inhibit the growth of a human colon carcinoma cell line in a concentration and time dependent manner. Rescue experiments using leucovorin and hypoxanthine-thymine medium were the first indication that epigallocatechin-3-gallate could disturb the folate metabolism within cells. Epigallocatechin-3-gallate increased the uptake of [H-3]-thymidine and showed synergy with 5-fluorouracil, while its inhibitory action was strengthened after treatment with hypoxanthine, which indicates that epigallocatechin-3-gallate decreases the cellular production of nucleotides, thus, disturbing DNA and RNA synthesis. In, addition to its effects on nucleotide biosynthesis, antifolate treatment has been linked to a decrease in cellular methylation. Here, we observed that epigallocatechin-3-gallate altered the p16 methylation pattern from methylated to unmethylated as a result of folic acid deprivation. Finally, we demonstrate that epigallocatechin-3-gallate causes adenosine to be released from the cells because it disrupts the purine metabolism. By binding to its specific receptors, adenosine can modulate different signalling pathways. This proposed mechanism should help us to understand most of the molecular and cellular effects described for this tea polyphenol
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Citation
International Journal of Biochemistry and Cell Biology. Volumen: 39 ,Nº12 , Año: 2007, Pags: 2215-2225
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Este ítem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by-nc-nd/4.0/