Inhibitory Effect of Electrolyzed Reduced Water on Tumor Angiogenesis(Molecular and Cell Biology)
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概要
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Vascular endothelial growth factor (VEGF) is a key mediator of tumor angiogenesis. Tumor cells are exposed to higher oxidative stress compared to normal cells. Numerous reports have demonstrated that the intracellular redox (oxidation/reduction) state is closely associated with the pattern of VEGF expression. Electrolyzed reduced water (ERW) produced near the cathode during the electrolysis of water scavenged intracellular H_2O_2 and decreased the release of H_2O_2 from a human lung adenocarcinoma cell line, A549, and down-regulated both VEGF transcription and protein secretion in a time-dependent manner. To investigate the signal transduction pathway involved in regulating VEGF expression, mitogen-activated kinase (MAPK) specific inhibitors, SB203580 (p38 MAPK inhibitor), PD98059 (ERK1/2 inhibitor) and JNKi (c-Jun N-terminal protein kinase inhibitor) were applied. The results showed that only PD98059 blocks VEGF expression, suggesting an important role for ERK1/2 in regulating VEGF expression in A549 cells. As well, ERW inhibited the activation of extracellular signal-regulated kinase (ERK) in a time-dependent manner. Co-culture experiments to analyze in vitro tubule formation assay revealed that A549 cell-derived conditioned medium significantly stimulated the formation of vascular tubules in all analyzed parameters; tubule total area, tubule junction, number of tubules, and total tubule length. ERW counteracted the effect of A549 cell-conditioned medium and decreased total tube length (p<0.01). The present study demonstrated that ERW down-regulated VEGF gene transcription and protein secretion through inactivation of ERK.
- 2008-01-01
著者
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Tachibana Hirofumi
Graduate School Of Genetic Resources Technology Kyushu University
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Jung Yeon
Graduate School Of Systems Life Sciences Kyushu University:key Laboratory Of The Ministry Of Educati
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Osada K
Yakult Central Inst. Tokyo Jpn
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Osada Kazuhiro
Laboratory Of Cellular Regulation Technology Graduate School Of Genetic Resources Technology Kyushu
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Osada Kazuhiro
Department Of Chemistry Science University Of Tokyo
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Kawahara Takeshi
Department of Medicine, Saiseikai Shiga Hospital
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SHIRAHATA Sanetaka
Graduate School of Genetic Resources Technology, Faculty of Agriculture, Kyushu University
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Abe Masumi
Department Of Genetic Resources Technology Faculty Of Agriculture Kyushu University
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Katakura Y
Fac. Of Agriculture Kyushu Univ.
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YE Jun
Graduate School of Systems Life Sciences, Kyushu University
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LI Yuping
Graduate School of Systems Life Sciences, Kyushu University
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HAMASAKI Takeki
Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University
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NAKAMICHI Noboru
Functional Water Cell Analysis Center Co., Ltd.
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KOMATSU Takaaki
Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University
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KASHIWAGI Taichi
Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University
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TERUYA Kiichiro
Graduate School of Systems Life Sciences, Kyushu University
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NISHIKAWA Ryuhei
Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University
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TOH Kazuko
Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University
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TIAN Huaize
Department of Genetic Resources Technology, Faculty of Agriculture, Kyushu University
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KABAYAMA Shigeru
Nihon Trim Co., Ltd.
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OTSUBO Kazumichi
Nihon Trim Co., Ltd.
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MORISAWA Shinkatsu
Nihon Trim Co., Ltd.
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KATAKURA Yoshinori
Graduate School of Systems Life Sciences, Kyushu University
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Osada Kazuhiro
Department Of Genetic Resources Technology Faculty Of Agriculture Kyushu University
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Tachibana Hirofumi
Division Of Bioresources And Bioenvironmental Science Kyushu University
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Tachibana Hirofumi
Faculty Of Agriculture Kyushu University
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Li Yuping
Graduate School Of Systems Life Sciences Kyushu University:school Of Life Sciences Nanchang Universi
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Toh Kazuko
Department Of Genetic Resources Technology Faculty Of Agriculture Kyushu University
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NAKAMICHI Noboru
Nihon Trim Co., Ltd.
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Teruya Kiichiro
Fac. Of Agriculture Kyushu Univ.
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Kabayama Shigeru
Nihon Trim Co. Ltd.
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Nakamichi Noboru
Nihon Trim Co. Ltd.
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Hamasaki Takeki
Dep. Of Genetic Resources Technol. Fac. Of Agriculture Kyushu Univ.
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Shirahata Sanetaka
Graduate School Of Systems Life Sciences Kyushu University:department Of Genetic Resources Technolog
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Shirahata S
Fac. Of Agriculture Kyushu Univ.
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Shirahata Sanetaka
Graduate School Of Genetic Resources Technology Faculty Of Agriculture Kyushu University
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Tomimatsu Kosuke
Graduate School Of Systems Life Sciences Kyushu Univ.
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Komatsu Takaaki
Department Of Genetic Resources Technology Faculty Of Agriculture Kyushu University
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Tachibana H
Faculty Of Agriculture Kyushu University
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Katakura Yoshinori
Dep. Of Genetic Resources Technol. Fac. Of Agriculture Kyushu Univ.
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Hamasaki Takeki
Department Of Genetic Resources Technology Faculty Of Agriculture Kyushu University
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Kashiwagi Taichi
Department Of Genetic Resources Technology Faculty Of Agriculture Kyushu University
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Ye Jun
Graduate School Of Systems Life Sciences Kyushu University:key Laboratory Of The Ministry Of Educati
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Kawahara Takeshi
Department Of Genetic Resources Technology Faculty Of Agriculture Kyushu University
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Kawahara Takeshi
Department Of Chemistry Biology And Marine Science Graduate School Of Science And Engineering Univer
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Tomimatsu Kosuke
Graduate School Of Systems Life Sciences Kyushu University
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Nishikawa Ryuhei
Department Of Genetic Resources Technology Faculty Of Agriculture Kyushu University
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Morisawa Shinkatsu
Nihon Trim Co. Ltd.
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Katakura Yoshinori
Graduate School Of Bioresource And Bioenvironmental Sciences Kyushu University
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Teruya Kiichiro
Graduate School Of Bioresource And Bioenvironmental Sciences Kyushu University
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Tian Huaize
Department Of Bioscience And Biotechnology Faculty Of Agriculture Kyushu University
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Hamasaki Takeki
Department Of Bioscience And Biotechnology Faculty Of Agriculture Kyushu University
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Otsubo Kazumichi
Nihon Trim Co. Ltd.
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SHIRAHATA Sanetaka
Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University
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