國家衛生研究院 NHRI:Item 3990099045/10993
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    题名: The inhibitory activity of gallic acid against DNA methylation: Application of gallic acid on epigenetic therapy of human cancers
    作者: Weng, YP;Hung, PF;Ku, WY;Chang, CY;Wu, BH;Wu, MH;Yao, JY;Yang, JR;Lee, CH
    贡献者: National Institute of Cancer Research
    摘要: 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.
    日期: 2018-01
    關聯: Oncotarget. 2018 Jan;9(1):361-374.
    Link to: http://dx.doi.org/10.18632/oncotarget.23015
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000419615500029
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85040625567
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