Anti-angiogenic Activity and Intracellular Distribution of Epigallocatechin-3-gallate Analogs
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概要
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Angiogenesis, a process of construction of new blood capillaries, is crucial for tumor progression and metastasis. Our previous studies demonstrated that a component of green tea, epigallocatechin-3-gallate (EGCG), suppressed angiogenesis and subsequent tumor growth. In this study, to elucidate the detailed mechanism of the anti-angiogenic effect of EGCG and to enhance the antiangiogenic activity of EGCG, we designed and synthesized EGCG derivatives and examined their biological effect and intracellular localization in human umbilical vein endothelial cells (HUVECs). EGCG derivatives aminopentyl dideoxyEGCG and aminopentyl dideoxygallocatechin-3-gallate (cis-APDOEGCG and trans-APDOEGCG) had an enhanced inhibitory effect on the proliferation when used at more than 30 μM. To elucidate antiangiogenic effect of EGCG, we used a 1 μM concentration for subsequent experiments where no effect on proliferation was observed. These EGCG derivatives showed a stronger inhibitory effect on migration, invasion, and tube formation by HUVECs than the non-derivatized EGCG. Furthermore, the derivatives induced a change in the distribution of F-actin and subsequent morphology of the HUVECs. Next, we synthesized fluorescent TokyoGreen-conjugated EGCG derivative (EGCG-TG) and observed the distribution in HUVECs under a confocal laser scanning microscope. Abundant fluorescence was observed in the cells after a 3-h incubation, and was localized in mitochondria as well as in cytoplasm. These results suggest that EGCG was incorporated into the HUVECs, that a portion of it entered into their mitochondria.
著者
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OKU Naoto
Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka
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Shimizu K
Department Of Pharmaceutics Hoshi University
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Oku Naoto
Department Of Medical Biochemistry And Coe Program In The 21st Century University Of Shizuoka School
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Asai Tomohiro
Department Of Medical Biochemistry And Global Coe University Of Shizuoka School Of Pharmaceutical Sc
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Asai T
Department Of Medical Biochemistry And Coe Program In The 21st Century University Of Shizuoka School
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Asai Tomohiro
Department Of Medical Biochemistry University Of Shizuoka School Of Pharmaceutical Sciences
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SHIMIZU Kosuke
Department of Medical Biochemistry and COE Program in the 21st Century, School of Pharmaceutical Sci
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Shimizu Kosuke
Department Of Medical Biochemistry University Of Shizuoka School Of Pharmaceutical Sciences
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Piyaviriyakul Suratsawadee
Department of Medical Biochemistry, Graduate School of Pharmaceutical Sciences, University of Shizuo
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Asakawa Tomohiro
Department of Synthetic Organic and Medicinal Chemistry, Graduate School of Pharmaceutical Sciences,
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Kan Toshiyuki
Department of Synthetic Organic and Medicinal Chemistry, Graduate School of Pharmaceutical Sciences,
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Siripong Pongpun
Research Division, National Cancer Institute Thailand
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Kan Toshiyuki
Department of Synthetic Organic and Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, University of Shizuoka
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Oku Naoto
Department of Medical Biochemistry, Graduate School of Pharmaceutical Sciences, University of Shizuoka
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Shimizu Kosuke
Department of Medical Biochemistry, Graduate School of Pharmaceutical Sciences, University of Shizuoka
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Asakawa Tomohiro
Department of Synthetic Organic and Medicinal Chemistry, Graduate School of Pharmaceutical Sciences, University of Shizuoka
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Piyaviriyakul Suratsawadee
Department of Medical Biochemistry, Graduate School of Pharmaceutical Sciences, University of Shizuoka
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OKU Naoto
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
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