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The inhibitory activity of gallic acid against DNA methylation: application of gallic acid on epigenetic therapy of human cancers.

ABSTRACT: Epigenome aberrations have been observed in tobacco-associated human malignancies. (-)-epigallocatechin-3-gallate (EGCG) has been proven to modulate gene expression by targeting DNA methyltransferases (DNMTs) through a proposed mechanism involving the gallate moiety of EGCG. We show that gallic acid (GA) changes the methylome of lung cancer and pre-malignant oral cell lines and markedly reduces both nuclear and cytoplasmic DNMT1 and DNMT3B within 1 week. GA exhibits stronger cytotoxicity against the lung cancer cell line H1299 than EGCG. We found that GA reactivates the growth arrest and DNA damage-inducible 45 (GADD45) signaling pathway may through the demethylation of CCNE2 and CCNB1 in H1299 cells. To improve the epigenetic anti-cancer activities of oolong tea, we identified a fungus, Aspergillus sojae which can efficiently increase the GA content in oolong tea via a 2-week fermentation process. The fungus dramatically increased GA up to 44.8 fold in the post-fermentation oolong tea extract (PFOTE), resulting in enhanced demethylation effects and a significant reduction in the nuclear abundances of DNMT1, DNMT3A, and DNMT3B in lung cancer cell lines. PFOTE also showed stronger anti-proliferation activities than oolong tea extract (OTE) and increased sensitivity to cisplatin in H1299 cells. In summary, we demonstrate the potent inhibitory effects of GA on the activities of DNMTs and provide a strong scientific foundation for the use of specialized fermented oolong tea high in GA as an effective dietary intervention strategy for tobacco-associated cancers.

SUBMITTER: Weng YP

PROVIDER: S-EPMC5787471 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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The inhibitory activity of gallic acid against DNA methylation: application of gallic acid on epigenetic therapy of human cancers.

Weng Yui-Ping YP Hung Pin-Feng PF Ku Wen-Yen WY Chang Chang-Yuan CY Wu Bo-Han BH Wu Ming-Han MH Yao Jau-Ying JY Yang Ji-Rui JR Lee Chia-Huei CH

Oncotarget 20171207 1

Epigenome aberrations have been observed in tobacco-associated human malignancies. (-)-epigallocatechin-3-gallate (EGCG) has been proven to modulate gene expression by targeting DNA methyltransferases (DNMTs) through a proposed mechanism involving the gallate moiety of EGCG. We show that gallic acid (GA) changes the methylome of lung cancer and pre-malignant oral cell lines and markedly reduces both nuclear and cytoplasmic DNMT1 and DNMT3B within 1 week. GA exhibits stronger cytotoxicity against ...[more]

PMID: 29416619

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Project description:Food supplements based on antioxidants and vitamins are often prescribed to correct inefficiencies in the human diet and delay diseases such as premature aging and alopecia (temporary or permanent hair loss), given the free radical scavenging activity of these biomolecules. By reducing the concentration of reactive oxygen species (ROS), which promote abnormal hair follicle cycling and morphology, follicle inflammation and oxidative stress are reduced, minimising the effects of these health issues. Gallic acid (GA), which is significantly present in gallnuts and in pomegranate root bark, and ferulic acid (FA), commonly found in brown rice and coffee seeds, are very important antioxidants for the preservation of hair colour, strength and growth. In this work, these two secondary phenolic metabolites were successfully extracted in the Aqueous Two-Phase Systems (ATPS) {ethyl lactate (1) + trisodium citrate (2) + water (3)} and {ethyl lactate (1) + tripotassium citrate (2) + water (3)} at 298.15 K and 0.1 MPa, moving towards the application of these ternary systems in extracting antioxidants from biowaste and their a posteriori processing as food supplements for hair fortification. The studied ATPS provided biocompatible and sustainable media for the extraction of gallic acid and ferulic acid, yielding low mass losses (<3%) and contributing to an eco-friendlier production of therapeutics. The most promising results were obtained for ferulic acid, which attained maximum partition coefficients (K) of 15 ± 5 and (3 ± 2) · 101 and maximum extraction efficiencies (E) of (92.7 ± 0.4)% and (96.7 ± 0.4)% for the longest tie-lines (TLL = 69.68 and 77.66 m%) in {ethyl lactate (1) + trisodium citrate (2) + water (3)} and {ethyl lactate (1) + tripotassium citrate (2) + water (3)}, respectively. Moreover, the effect of pH on the UV-Vis absorbance spectra was studied for all the biomolecules to minimise errors in solute quantification. Both GA and FA were found to be stable at the used extractive conditions.

Dataset Information

The inhibitory activity of gallic acid against DNA methylation: application of gallic acid on epigenetic therapy of human cancers.

Publications

The inhibitory activity of gallic acid against DNA methylation: application of gallic acid on epigenetic therapy of human cancers.

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