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Journal ArticleDOI

Theaflavin-Containing Black Tea Extract: A Potential DNA Methyltransferase Inhibitor in Human Colon Cancer Cells and Ehrlich Ascites Carcinoma-Induced Solid Tumors in Mice.

TL;DR: It was found that theaflavin prevented cell proliferation and inhibited tumor progression as well and has a potential role as a DNMT inhibitor in HCT-116 cell line and EAC induced solid tumors in mice.
Abstract: Tea is the most popularly consumed beverage in the world. Theaflavin and thearubigins are the key bioactive compounds of black tea that have anticarcinogenic properties as reported in several studies. However, the epigenetic potential of these compounds has not yet been explored. DNA methyltransferase (DNMT) enzymes induce methylation of DNA at cytosine residues and play a significant role in epigenetic regulation and cancer therapy. The present study has explored the role of black tea as a DNMT inhibitor in the prevention of cancer. Herein, the effect of theaflavin has been studied in colon cancer cell line (HCT-116) and EAC-induced solid tumors in mice. It was found that theaflavin prevented cell proliferation and inhibited tumor progression as well. In silico study showed that theaflavin interacted with DNMT1 and DNMT3a enzymes and blocked their activity. Theaflavin also decreased DNMT activity In Vitro and In Vivo as evident from the DNMT activity assay. Results of immunohistochemistry revealed that theaflavin reduced DNMT expression in the tumors of mice. Taken together, our findings showed that theaflavin has a potential role as a DNMT inhibitor in HCT-116 cell line and EAC induced solid tumors in mice.
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Journal ArticleDOI
TL;DR: In this paper, the authors reviewed and discussed the recent literature on the health benefits of tea and its compounds, and specifically explored the molecular mechanisms involved, including the regulation of several classical signaling pathways, such as nuclear factor-κB, AMP activated protein kinase (AMPK), and wingless/integrated (Wnt) signaling.

43 citations

Journal ArticleDOI
TL;DR: In this article, a review summarizes the current in vitro and in vivo evidence available investigating the anti-cancer effects of theaflavins across various cancer cell lines and animal models.
Abstract: Cancer is a disease characterized by aberrant proliferative and apoptotic signaling pathways, leading to uncontrolled proliferation of cancer cells combined with enhanced survival and evasion of cell death. Current treatment strategies are sometimes ineffective in eradicating more aggressive, metastatic forms of cancer, indicating the need to develop novel therapeutics targeting signaling pathways which are essential for cancer progression. Historically, plant-derived compounds have been utilized in the production of pharmaceuticals and chemotherapeutic compounds for the treatment of cancer, including paclitaxel and docetaxel. Theaflavins, phenolic components present in black tea, have demonstrated anti-cancer potential in cell cultures in vitro and in animal studies in vivo. Theaflavins have been shown to inhibit proliferation, survival, and migration of many cancer cellswhile promoting apoptosis. Treatment with theaflavins has been associated with increased levels of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspases-3, -7, -8, and -9, all markers of apoptosis, and increased expression of the proapoptotic marker Bcl-2-associated X protein (Bax) and concomitant reduction in the antiapoptotic marker B-cell lymphoma 2 (Bcl-2). Additionally, theaflavin treatment reduced phosphorylated Akt, phosphorylated mechanistic target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and c-Myc levels with increased expression of the tumour suppressor p53. This review summarizes the current in vitro and in vivo evidence available investigating the anti-cancer effects of theaflavins across various cancer cell lines and animal models.

16 citations

Journal ArticleDOI
TL;DR: In this article, the authors discuss the composition, characterization, bioconversion and value added product generation from spent tea leaves while highlighting prospective applications of STL in developing battery electrodes, nanocatalysts, insulation materials and edible bioactive peptides.

15 citations

Journal ArticleDOI
TL;DR: The role dietary polyphenols plays in restoring epigenetic alterations in cancer cells with a particular focus on DNA methylation and histone modifications was summarized and the potential of polyphenolic compounds as an alternative therapeutic approach in cancer is highlighted.
Abstract: Human diseases such as cancer can be caused by aberrant epigenetic regulation. Polyphenols play a major role in mammalian epigenome regulation through mechanisms and proteins that remodel chromatin. In fruits, seeds, and vegetables, as well as food supplements, polyphenols are found. Compounds such as these ones are powerful anticancer agents and antioxidants. Gallic acid, kaempferol, curcumin, quercetin, and resveratrol, among others, have potent anti-tumor effects by helping reverse epigenetic changes associated with oncogene activation and tumor suppressor gene inactivation. The role dietary polyphenols plays in restoring epigenetic alterations in cancer cells with a particular focus on DNA methylation and histone modifications was summarized. We also discussed how these natural compounds modulate gene expression at the epigenetic level and described their molecular targets in cancer. It highlights the potential of polyphenols as an alternative therapeutic approach in cancer since they modulate epigenetic activity.

14 citations

DOI
12 Nov 2021
TL;DR: The main stages involved in production of Camellia sinensis teas following a description of their main bioactive compounds, biological properties, stability and bioaccessibility was provided by focusing on novel findings and innovations published in scientific literature over the last five years as discussed by the authors.
Abstract: The plant Camellia sinensis is the source of different teas (white, green, yellow, oolong, black, and pu-ehr) consumed worldwide, which are classified by the oxidation degree of their bioactive compounds. The sensory (taste, aroma, and body of the drink) and functional properties of teas are affected by the amount of methylxanthines (caffeine and theobromine), amino acids ( l -theanine) and reducing sugars in their composition. Additionally, flavan-3-ols, mainly characterized by epicatechins, catechins, and their derivatives, represent on average, 60% of the bioactive compounds in teas. These secondary metabolites from teas are widely recognized for their antioxidant, anti-cancer, and anti-inflammatory properties. Thus, Camellia sinensis extracts and their isolated compounds have been increasingly used by the food industry. However, bioactive compounds are very susceptible to the oxidation caused by processing and degradation under physiological conditions of gastrointestinal digestion. In this context, new approaches/technologies have been developed for the preservation of these compounds. This review presents the main stages involved in production of Camellia sinensis teas following a description of their main bioactive compounds, biological properties, stability and bioaccessibility. Besides, and updated view of Camellia sinensis teas in the field of food science and technology was provided by focusing on novel findings and innovations published in scientific literature over the last five years.

14 citations

References
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Journal Article
TL;DR: In the laboratory, the laboratory investigates several areas, including protein-ligand docking, protein-protein docking, and complex molecular assemblies, as well as developing a number of computational tools such as molecular surfaces, phenomenological potentials, various docking and visualization programs which are used in conjunction with programs developed by others.
Abstract: One of the challenges in bio-computing is to enable the efficient use and inter-operation of a wide variety of rapidly-evolving computational methods to simulate, analyze, and understand the complex properties and interactions of molecular systems. In our laboratory we investigates several areas, including protein-ligand docking, protein-protein docking, and complex molecular assemblies. Over the years we have developed a number of computational tools such as molecular surfaces, phenomenological potentials, various docking and visualization programs which we use in conjunction with programs developed by others. The number of programs available to compute molecular properties and/or simulate molecular interactions (e.g., molecular dynamics, conformational analysis, quantum mechanics, distance geometry, docking methods, ab-initio methods) is large and growing rapidly. Moreover, these programs come in many flavors and variations, using different force fields, search techniques, algorithmic details (e.g., continuous space vs. discrete, Cartesian vs. torsional). Each variation presents its own characteristic set of advantages and limitations. These programs also tend to evolve rapidly and are usually not written as components, making it hard to get them to work together.

2,665 citations

Journal Article
Mingzhu Fang1, Yimin Wang1, Ni Ai1, Zhe Hou1, Yi Sun1, Hong Lu1, William J. Welsh1, Chung S. Yang1 
TL;DR: It is reported herein that (-)-epigallocatechin-3-gallate (EGCG), the major polyphenol from green tea, can inhibit DNMT activity and reactivate methylation-silenced genes in cancer cells and the potential use of EGCG for the prevention or reversal of related gene-silencing in the prevention of carcinogenesis is suggested.
Abstract: Hypermethylation of CpG islands in the promoter regions is an important mechanism to silence the expression of many important genes in cancer. The hypermethylation status is passed to the daughter cells through the methylation of the newly synthesized DNA strand by 5-cytosine DNA methyltransferase (DNMT). We report herein that (-)-epigallocatechin-3-gallate (EGCG), the major polyphenol from green tea, can inhibit DNMT activity and reactivate methylation-silenced genes in cancer cells. With nuclear extracts as the enzyme source and polydeoxyinosine-deoxycytosine as the substrate, EGCG dose-dependently inhibited DNMT activity, showing competitive inhibition with a K(i) of 6.89 microM. Studies with structural analogues of EGCG suggest the importance of D and B ring structures in the inhibitory activity. Molecular modeling studies also support this conclusion, and suggest that EGCG can form hydrogen bonds with Pro(1223), Glu(1265), Cys(1225), Ser(1229), and Arg(1309) in the catalytic pocket of DNMT. Treatment of human esophageal cancer KYSE 510 cells with 5-50 microM of EGCG for 12-144 h caused a concentration- and time-dependent reversal of hypermethylation of p16(INK4a), retinoic acid receptor beta (RARbeta), O(6)-methylguanine methyltransferase (MGMT), and human mutL homologue 1 (hMLH1) genes as determined by the appearance of the unmethylation-specific bands in PCR. This was accompanied by the expression of mRNA of these genes as determined by reverse transcription-PCR. The re-expression of RARbeta and hMLH1 proteins by EGCG was demonstrated by Western blot. Reactivation of some methylation-silenced genes by EGCG was also demonstrated in human colon cancer HT-29 cells, esophageal cancer KYSE 150 cells, and prostate cancer PC3 cells. The results demonstrate for the first time the inhibition of DNA methylation by a commonly consumed dietary constituent and suggest the potential use of EGCG for the prevention or reversal of related gene-silencing in the prevention of carcinogenesis.

1,019 citations

Reference EntryDOI

900 citations


"Theaflavin-Containing Black Tea Ext..." refers methods in this paper

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  • ...The total phenolic content of the TF extract was estimated with the Folin-Ciocalteu colorimetric method, based on the method of Waterhouse 2002 (12)....

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Journal Article
TL;DR: Inadequate training or inattention to detail during this aspect of a study may result in unintentional adverse effects on experimental animals and confounded results.
Abstract: Administration of substances to laboratory animals requires careful consideration and planning to optimize delivery of the agent to the animal while minimizing potential adverse experiences from the procedure. For all species, many different routes are available for administration of substances. The research team and IACUC members should be aware of reasons for selecting specific routes and of training and competency necessary for personnel to use these routes effectively. Once a route is selected, issues such as volume of administration, site of delivery, pH of the substance, and other factors must be considered to refine the technique. Inadequate training or inattention to detail during this aspect of a study may result in unintentional adverse effects on experimental animals and confounded results.

701 citations

Journal ArticleDOI
TL;DR: This article summarizes available data on the chemopreventive efficacies of tea polyphenols, curcumin and ellagic acid in various model systems and focuses upon the anticarcinogenic activity of these polyphenol and their proposed mechanism(s) of action.
Abstract: In recent years, the concept of chemoprevention has matured to be considered as a practical option to reduce the occurrence of cancer (1–5). Chemoprevention—the use of natural and/or synthetic compounds to intervene in the early precancerous stages of carcinogenesis before the onset of invasive disease—offers a viable approach to define substances, either food components or pharmaceuticals, which can prevent, delay, or completely halt the process of carcinogenesis. Often chemoprevention is referred to as “prevention by delay.”

608 citations