Inhibitory Effect of Electrolyzed Reduced Water on Tumor Angiogenesis

Abstract

Tumor angiogenesis, the formation of new blood capillaries by vascular endothelial cells from existing vessels, is an important mechanism for supplying nutrients, oxygen, growth factors and others to tumor cells. Tumor cells trigger angiogenesis by secreting angiogenic factors, especially vascular endothelial growth factor (VEGF-A), 1) which plays an important role in the regulation of normal and abnormal angiogenesis.2) VEGF-A (commonly known as VEGF) was first reported as a vascular permeability-inducing factor secreted by tumor cells, and referred to as vascular permeability factor (VPF). Reactive oxygen species (ROS) are suggested to play an important role in angiogenesis. 10) Furthermore, there is increasing evidence of the involvement of H 2 O 2 in the regulation of angiogenesis.9,11-13) As well, a variety of cell lines derived from human tumors has been shown to produce large amounts of H 2 O 2 .14) Constitutive surveillance for cellular protection against oxidative stress is conferred by intracellular antioxidative agents.15) Excess amounts of ROS are toxic and cause a reduction of intracellular antioxidant levels.16) It has been reported that pretreatment of the heart with exogenous antioxidants improved its condition as a result of reducing ROS production.17) The VEGF-A gene is one that has its expression regulated by ROS, especially by H 2 O 2 . Additional data support that VEGF-A mRNA is up-regulated by H 2 O 2 in a dose-and time-dependent manner. 18,19) Taken together, these suggest that some endogenous as well as exogenous antioxidative agents can be used to regulate VEGF-A gene expression and/or H 2 O 2 production for therapeutic purposes.Electrolyzed reduced water (ERW) has attracted much attention because of its antioxidative potential. Water electrolysis typically produces two forms of water: reduced or alkaline (high pH) water near the cathode and an oxidized or acid (low pH) water near the anode. Applications of oxidized

Suppressive effects of electrolyzed reduced water on alloxan-induced apoptosis and type 1 diabetes mellitus

“…From these results, the candidate active substance(s) may be dissolved hydrogen and Pt. We proposed an active hydrogen metal nanoparticle reduced water hypothesis that electrolysis of water produces metal nanopartilces from metal ions which directly scavenges ROS and also activate hydrogen molecule to active hydrogen (hydrogen atom) to scavenge ROS in ERW (Shirahata et al 1997;Ye et al 2008;Shirahata 2002Shirahata , 2004. We demonstrated that Pt nanoparticles exhibited a good catalysis activity to scavenge O 2 Á -, H 2 O 2 , and ÁOH and suppressed oxygen-stress damages in cultured cells .…”

“…Further detail of the device is given elsewhere (Ye et al 2008). Sample waters were stored in closed glass bottles at 4°C and neutralized with 12 mM HEPES buffer (pH 7.4) when medium was prepared.…”

Physico-Chemical, Biological and Therapeutic Characteristics of Electrolyzed Reduced Alkaline Water (ERAW)

“…The action of H 2 also goes beyond just elimination of excess ROS. A number of reports have shown an effect of H 2 on the regulation of gene expression, acting directly on cellular signalling pathways that are stimulated by excess ROS [18,41,42]. However, many of the reactions occurring in the presence of small quantities of H 2 still need to be elucidated [38].…”

Effect of electrolyzed water produced using carbon electrodes on HeLa cell proliferation

“…Electrochemically reduced water has been shown to exert anti-cancer effects. For example, electrochemically reduced water produced near the cathode during the electrolysis of ultrapure water containing sodium hydroxide at 100 V for 60 min using an electrolyzing device equipped with platinum-coated titanium electrodes suppressed tumor angiogenesis in human lung adenocarcinoma A549 cells and tumor invasion in human fibrosarcoma HT1080 cells (6,7). Recently, several researchers have reported the generation of electrolyzed water of neutral pH by an electrolysis chamber without a diaphragm.…”