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      The Green Tea Catechin Epigallocatechin Gallate (EGCG) Blocks Cell Motility, Chemotaxis and Development in Dictyostelium discoideum

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          Abstract

          Catechins, flavanols found at high levels in green tea, have received significant attention due to their potential health benefits related to cancer, autoimmunity and metabolic disease, but little is known about the mechanisms by which these compounds affect cellular behavior. Here, we assess whether the model organism Dictyostelium discoideum is a useful tool with which to characterize the effects of catechins. Epigallocatechin gallate (EGCG), the most abundant and potent catechin in green tea, has significant effects on the Dictyostelium life cycle. In the presence of EGCG aggregation is delayed, cells do not stream and development is typically stalled at the loose aggregate stage. The developmental effects very likely result from defects in motility, as EGCG reduces both random movement and chemotaxis of Dictyostelium amoebae. These results suggest that catechins and their derivatives may be useful tools with which to better understand cell motility and development in Dictyostelium and that this organism is a useful model to further characterize the activities of catechins.

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          Most cited references 42

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          The genome of the social amoeba Dictyostelium discoideum.

          The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.
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            Cancer prevention by tea: animal studies, molecular mechanisms and human relevance.

            Extracts of tea, especially green tea, and tea polyphenols have been shown to inhibit the formation and development of tumours at different organ sites in animal models. There is considerable evidence that tea polyphenols, in particular (-)-epigallocatechin-3-gallate, inhibit enzyme activities and signal transduction pathways, resulting in the suppression of cell proliferation and enhancement of apoptosis, as well as the inhibition of cell invasion,angiogenesis and metastasis. Here, we review these biological activities and existing data relating tea consumption to human cancer risk in an attempt to understand the potential use of tea for cancer prevention.
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              Inhibitory effects of oolong tea polyphenols on pancreatic lipase in vitro.

              Fifty-four polyphenols isolated from tea leaves were evaluated for their inhibitory activities against pancreatic lipase, the key enzyme of lipid absorption in the gut. (-)-Epigallocatechin 3-O-gallate (EGCG), which is one of major polyphenols in green tea, showed lipase inhibition with an IC50 of 0.349 microM. Moreover, flavan-3-ol digallate esters, such as (-)-epigallocatechin-3,5-digallate, showed higher activities of inhibition on lipase with an IC50 of 0.098 microM. On the other hand, nonesterified flavan-3-ols, such as (+)-catechin, (-)-epicatechin, (+)-gallocatechin, and (-)-epigallocatechin, showed zero and/or the lowest activities against pancreatic lipase (IC50 > 20 microM). These data suggested that the presence of galloyl moieties within the structure was required for enhancement of pancreatic lipase inhibition. It is well-known that flavan-3-ols are polymerized by polyphenol oxidase and/or heating in a manufacturing process of oolong tea. Oolonghomobisflavans A and B and oolongtheanin 3'-O-gallate, which are typical in oolong tea leaves, showed strong inhibitory activities with IC50 values of 0.048, 0.108, and 0.068 microM, respectively, even higher than that of EGCG. The oolong tea polymerized polyphenols (OTPP) were prepared for the assay from oolong tea extract, from which the preparation effectively subtracted the zero and/or less-active monomeric flavan-3-ols by preparative high-performance liquid chromatography. The weight-average molecular weight (Mw) and number-average molecular-weight (Mn) values of OTPP were 2017 and 903, respectively, by using gel permeation choromatography. OTPP showed a 5-fold stronger inhibition against pancreatic lipase (IC50 = 0.28 microg/mL) by comparison with that of the tannase-treated OTPP (IC50 = 1.38 microg/mL). These data suggested that the presence of galloyl moieties within their chemical structures and/or the polymerization of flavan-3-ols were required for enhancement of pancreatic lipase inhibition.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                14 March 2013
                : 8
                : 3
                Affiliations
                [1 ]Department of Biological Sciences, Colorado Mesa University, Grand Junction, Colorado, United States of America
                [2 ]Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan
                [3 ]Research Center for Complex Systems Biology, The University of Tokyo, Tokyo, Japan
                [4 ]PRESTO, Japan Science and Technology Agency, Tokyo, Japan
                Cardiff University, United Kingdom
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: KJM AN ANI NS SS. Performed the experiments: AN ANI NS. Analyzed the data: KJM AN ANI NS SS. Wrote the paper: KJM SS.

                Article
                PONE-D-12-26961
                10.1371/journal.pone.0059275
                3597604
                23516620

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Pages: 13
                Funding
                The work in the Sawai Lab was supported by JSPS Grant-in-Aid for Young Scientists (A) (22680024), Grant-in-Aid for Scientific Research on Innovative Areas (23111506), JST PRESTO program and in part by Human Frontier Science Program (RGY 70/2008) and Platform for Dynamic Approaches to Living Systems from MEXT, Japan. AN was supported by JSPS Grant-in-Aid for Research Activity Start-up (23870006). KJM was supported by the Colorado Mesa University (CMU) Biology Department and by Faculty Development Awards from CMU. ANI was supported by an undergraduate research award from Beta Beta Beta Honor Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Biochemistry
                Biophysics
                Cell Motility
                Developmental Biology
                Molecular Development
                Signaling
                Morphogenesis
                Model Organisms
                Protozoan Models
                Dictyostelium Discoideum
                Molecular Cell Biology
                Signal Transduction
                Medicine
                Drugs and Devices
                Drug Research and Development
                Drug Discovery

                Uncategorized

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