Inhibitory effect of electrolyzed reduced water on tumor angiogenesis

Jun Ye, Yuping Li, Takeki Hamasaki, Noboru Nakamichi, Takaaki Komatsu, Taichi Kashiwagi, Kiichiro Teruya, Ryuhei Nishikawa, Takeshi Kawahara, Kazuhiro Osada, Kazuko Toh, Masumi Abe, Huaize Tian, Shigeru Kabayama, Kazumichi Otsubo, Shinkatsu Morisawa, Yoshinori Katakura, Sanetaka Shirahata

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DOI: 10.1248/bpb.31.19 DOI is the universal ID for this study.

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Abstract:

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(2)O(2) and decreased the release of H(2)O(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.

Publish Year 2008
Country Japan
Rank Positive
Journal Biological and Pharmaceutical Bulletin
Primary Topic Whole Body
Secondary Topic Cancer
Model Cell Culture
Tertiary Topic Oncogenesis
Vehicle Water (Electrolysis)
pH Alkaline
Application Irrigation
Comparison
Complement