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      Epigallocatechin Gallate-Mediated Alteration of the MicroRNA Expression Profile in 5α-Dihydrotestosterone-Treated Human Dermal Papilla Cells

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          Abstract

          Background

          Dihydrotestosterone (DHT) induces androgenic alopecia by shortening the hair follicle growth phase, resulting in hair loss. We previously demonstrated how changes in the microRNA (miRNA) expression profile influenced DHT-mediated cell death, cell cycle arrest, cell viability, the generation of reactive oxygen species (ROS), and senescence. Protective effects against DHT have not, however, been elucidated at the genome level.

          Objective

          We showed that epigallocatechin gallate (EGCG), a major component of green tea, protects DHT-induced cell death by regulating the cellular miRNA expression profile.

          Methods

          We used a miRNA microarray to identify miRNA expression levels in human dermal papilla cells (DPCs). We investigated whether the miRNA expression influenced the protective effects of EGCG against DHT-induced cell death, growth arrest, intracellular ROS levels, and senescence.

          Results

          EGCG protected against the effects of DHT by altering the miRNA expression profile in human DPCs. In addition, EGCG attenuated DHT-mediated cell death and growth arrest and decreased intracellular ROS levels and senescence. A bioinformatics analysis elucidated the relationship between the altered miRNA expression and EGCG-mediated protective effects against DHT.

          Conclusion

          Overall, our results suggest that EGCG ameliorates the negative effects of DHT by altering the miRNA expression profile in human DPCs.

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          Most cited references 41

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          MicroRNA-210 regulates cancer cell proliferation through targeting fibroblast growth factor receptor-like 1 (FGFRL1).

          The importance of microRNAs (miRNAs) in human malignancies has been well recognized. Here, we report that the expression of microRNA-210 (miR-210) is down-regulated in human esophageal squamous cell carcinoma and derived cell lines. Marked decreases in the level of miR-210 were observed especially in poorly differentiated carcinomas. We found that miR-210 inhibits cancer cell survival and proliferation by inducing cell death and cell cycle arrest in G(1)/G(0) and G(2)/M. Finally, we identified fibroblast growth factor receptor-like 1 (FGFRL1) as a target of miR-210 in esophageal squamous cell carcinoma and demonstrated that FGFRL1 accelerates cancer cell proliferation by preventing cell cycle arrest in G(1)/G(0). Taken together, our findings show an important role for miR-210 as a tumor-suppressive microRNA with effects on cancer cell proliferation.
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            Green tea polyphenol (-)-epigallocatechin-3-gallate treatment of human skin inhibits ultraviolet radiation-induced oxidative stress.

            The use of naturally occurring botanicals with substantial antioxidant activity to afford protection to human skin against UV damage is receiving increasing attention. The green tea constituent (-)-epigallocatechin-3-gallate (EGCG) is a potent antioxidant and has shown remarkable preventive effects against photocarcinogenesis and phototoxicity in mouse models. In this study we have investigated the effects of topical application of EGCG, the major polyphenol present in green tea, to human skin before UV irradiation on UV-induced markers of oxidative stress and antioxidant enzymes. Using immunohistochemistry and analytical enzyme assays, we found that application of EGCG (mg/cm(2) skin) before a single UV exposure of 4x minimal erythema dose (MED) markedly decreases UV-induced production of hydrogen peroxide (68-90%, P < 0.025-0.005) and nitric oxide (30-100%, P < 0.025-0.005) in both epidermis and dermis in a time-dependent manner. EGCG pretreatment also inhibits UV-induced infiltration of inflammatory leukocytes, particularly CD11b(+) cells (a surface marker of monocytes/macrophages and neutrophils), into the skin, which are considered to be the major producers of reactive oxygen species. EGCG treatment was also found to inhibit UV-induced epidermal lipid peroxidation at each time point studied (41-84%, P < 0.05). A single UV exposure of 4x MED to human skin was found to increase catalase activity (109-145%) and decrease glutathione peroxidase (GPx) activity (36-54%) and total glutathione (GSH) level (13-36%) at different time points studied. Pretreatment with EGCG was found to restore the UV-induced decrease in GSH level and afforded protection to the antioxidant enzyme GPx. Further studies are warranted to study the preventive effects of EGCG against multiple exposures to UV light of human skin.
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              Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy.

              Green tea catechins, especially epigallocatechin-3-gallate (EGCG), have been associated with cancer prevention and treatment. This has resulted in an increased number of studies evaluating the effects derived from the use of this compound in combination with chemo/radiotherapy. This review aims at compiling latest literature on this subject. Keywords including EGCG, cancer, chemotherapy, radiotherapy and side effects, were searched using PubMed and ScienceDirect databases to identify, analyze, and summarize the research literature on this topic. Most of the studies on this subject up to date are preclinical. Relevance of the findings, impact factor, and date of publication were critical parameters for the studies to be included in the review. Additive and synergistic effects of EGCG when combined with conventional cancer therapies have been proposed, and its anti-inflammatory and antioxidant activities have been related to amelioration of cancer therapy side effects. However, antagonistic interactions with certain anticancer drugs might limit its clinical use. The use of EGCG could enhance the effect of conventional cancer therapies through additive or synergistic effects as well as through amelioration of deleterious side effects. Further research, especially at the clinical level, is needed to ascertain the potential role of EGCG as adjuvant in cancer therapy. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
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                Author and article information

                Journal
                Ann Dermatol
                Ann Dermatol
                AD
                Annals of Dermatology
                Korean Dermatological Association; The Korean Society for Investigative Dermatology
                1013-9087
                2005-3894
                June 2016
                25 May 2016
                : 28
                : 3
                : 327-334
                Affiliations
                Korea Institute for Skin and Clinical Sciences and Molecular-Targeted Drug Research Center, Konkuk University, Seoul, Korea.
                [1 ]Department of Dermatology, Konkuk University School of Medicine, Seoul, Korea.
                [2 ]KISCS Incorporated, Cheongju, Korea.
                Author notes
                Corresponding author: Hwa Jun Cha, Korea Institute for Skin and Clinical Sciences and Molecular-Targeted Drug Research Center, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea. Tel: 82-2-450-3743, Fax: 82-2-3437-8360, hjcha@ 123456konkuk.ac.kr

                *These authors contributed equally to this work.

                Article
                10.5021/ad.2016.28.3.327
                4884709
                27274631
                Copyright © 2016 The Korean Dermatological Association and The Korean Society for Investigative Dermatology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Funding
                Funded by: Konkuk University, CrossRef http://dx.doi.org/10.13039/501100002641;
                Funded by: Ministry of Science, ICT and Future Planning, CrossRef http://dx.doi.org/10.13039/501100003621;
                Award ID: 20110028646
                Funded by: Ministry of Health and Welfare, CrossRef http://dx.doi.org/10.13039/501100003625;
                Award ID: HN13C0075
                Categories
                Original Article

                Dermatology

                human dermal papilla cells, epigallocatechin gallate, micrornas

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