Suppressive effects of electrochemically reduced water on matrix metalloproteinase-2 activities and in vitro invasion of human fibrosarcoma HT1080 cells

Abstract

It has been demonstrated that hydrogen peroxide (H(2)O(2)) is directly associated with elevated matrix metalloproteinase-2 (MMP-2) expression in several cell lines. Electrochemically reduced water (ERW), produced near the cathode during electrolysis, and scavenges intracellular H(2)O(2) in human fibrosarcoma HT1080 cells. RT-PCR and zymography analyses revealed that when HT1080 cells were treated with ERW, the gene expression of MMP-2 and membrane type 1 MMP and activation of MMP-2 was repressed, resulting in decreased invasion of the cells into matrigel. ERW also inhibited H(2)O(2)-induced MMP-2 upregulation. To investigate signal transduction involved in MMP-2 downregulation, mitogen-activated protein kinase (MAPK)-specific inhibitors, SB203580 (p38 MAPK inhibitor), PD98059 (MAPK/extracellular regulated kinase kinase 1 inhibitor) and c-Jun NH(2)-terminal kinase inhibitor II, were used to block the MAPK signal cascade. MMP-2 gene expression was only inhibited by SB203580 treatment, suggesting a pivotal role of p38 MAPK in regulation of MMP-2 gene expression. Western blot analysis showed that ERW downregulated the phosphorylation of p38 both in H(2)O(2)-treated and untreated HT1080 cells. These results indicate that the inhibitory effect of ERW on tumor invasion is due to, at least in part, its antioxidative effect.

Electrochemically Reduced Water Protects Neural Cells from Oxidative Damage

“…Further studies with N1E-115 cells demonstrated that the suppressive effect of ERW stemmed from its ROS scavenging ability. This finding is in accordance with the previous reports obtained from pancreatic β -cell HIT-T15 cells [ 15 , 19 ], human lung carcinoma A549 cells [ 41 ], HT1080 tumor cells [ 24 ], and diabetic db/db mice [ 48 ].…”

“…ERW contains a high concentration of dissolved hydrogen (0.4–0.9 ppm) and a small amount of platinum nanoparticles (Pt nps, 0.1–2.5 ppb), both of which exhibit ROS-scavenging ability [ 11 , 16 , 17 ]. Neutralized ERW has been shown to exhibit H 2 O 2 -scavenging activity which is correlated with protection of DNA [ 18 , 19 ] and carbon tetrachloride induced liver damage [ 20 ], lifespan extension of Caenorhabditis elegans [ 16 , 21 ], alloxan-induced type 1 diabetes [ 15 , 19 ], hemodialysis-induced oxidative stress during end-stage renal disease [ 22 , 23 ], and inhibitory effects of HT1080 tumor cell invasion [ 24 ]. ERW, in combination with glutathione, induced human leukemia HL-60 apoptotic cell death whereas a cytotoxic effect was not observed in normal peripheral blood mononuclear cells [ 25 ].…”

Oncogenic Ras/ERK Signaling Activates CDCP1 to Promote Tumor Invasion and Metastasis

“…5C and D). The suppressive effect of the MMP2/MMP9 inhibitor II in cell invasion was also observed in A549 cells, H-Ras-12V-expressing H322Fyn cells and HT1080 cells, of which invasion was reported to be regulated by MMP2 and MMP9 (33,34) (Supplementary Fig. S8).…”

Low Concentration Platinum Nanoparticles Effectively Scavenge Reactive Oxygen Species in Rat Skeletal L6 Cells

“…According to reports, internalized PtNPs are estimated to be approximately 8,000 particles per cell when using 2 nm PtNPs at 10 mg/l; this demonstrates strong ROS scavenging activity when these PtNPs are added to the cells. By simple calculation, the internalized PtNPs will be 8 particles per cell when 10 −3 mg/l PtNPs is added to the cells [14,50]. Therefore, it is unlikely that such a small number of internalized PtNPs could directly exert strong ROS scavenging ability in the present study.…”