Antitumor effects of nano-bubble hydrogen-dissolved water are enhanced by coexistent platinum colloid and the combined hyperthermia with apoptosis-like cell death.
In order to erase reactive oxygen species (ROS) related with the proliferation of tumor cells by reducing activity of hydrogen, we developed functional water containing nano-bubbles (diameters: <900 nm for 71%/population) hydrogen of 1.1-1.5 ppm (the theoretical maximum: 1.6 ppm) with a reducing ability (an oxidation-reduction potential -650 mV, normal water: +100-200 mV) using a microporous-filter hydrogen-jetting device. We showed that hydrogen water erased ROS indispensable for tumor cell growth by ESR/spin trap, the redox indicator CDCFH-DA assay, and was cytotoxic to Ehrlich ascites tumor cells as assessed by WST-8 assay, crystal violet dye stain and scanning electron microscopy, after 24-h or 48-h incubation sequent to warming at 37°C or 42°C. Hydrogen water supplemented with platinum colloid (0.3 ppm Pt in 4% polyvinylpyrrolidone) had more antitumor activity than hydrogen water alone, mineral water alone (15.6%), hydrogen water plus mineral water, or platinum colloid alone as observed by decreased cell numbers, cell shrinkage and pycnosis (nuclear condensation)/karyorrhexis (nuclear fragmentation) indicative of apoptosis, together with cell deformation and disappearance of microvilli on the membrane surface. These antitumor effects were promoted by combination with hyperthermia at 42°C. Thus, the nano-bubble hydrogen water with platinum colloid is potent as an anti-tumor agent.
Osaka Buturyo College, Nishi-ku, Sakai 593-8328, Japan.
Ryoko
R
Asada
Katsuhiro
K
Kageyama
Hiroshi
H
Tanaka
Hisakazu
H
Matsui
Masatsugu
M
Kimura
Yasukazu
Y
Saitoh
Nobuhiko
N
Miwa
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003102:Colloids / Q000008:administration & dosage / Q000494:pharmacology; D003131:Combined Modality Therapy; D004357:Drug Synergism; D005740:Gases / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006859:Hydrogen / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D006979:Hyperthermia, Induced / Q000379:methods; D008954:Models, Biological; D053758:Nanoparticles; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D010984:Platinum / Q000008:administration & dosage* / Q000494:pharmacology; D012995:Solubility; D014867:Water / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
D003102:Colloids; D005740:Gases; D014867:Water; D010984:Platinum; D006859:Hydrogen