title: Transient generation of hydrogen peroxide is responsible for carcinostatic effects of hydrogen combined with platinum nanocolloid, together with increases intracellular ROS, DNA cleavages, and proportion of G2/M-phase.
abstract: In our previous study, we demonstrated that combined treatment with hydrogen (H2) and platinum nanocolloid (Pt-nc) exerted markedly antiproliferative effects on cancer cells compared with each treatment alone. However, because the related mechanisms remain unclear, we investigated carcinostatic mechanisms of the combined treatment with H2 + Pt-nc. Significant suppression of cell proliferation was confirmed at 52 h following combined treatment, and the similar effect was also observed by the 30- or 40-min transient treatment with H2 + Pt-nc. The transient treatments led to changes in cell size and morphology, loss of microvilli, and apoptosis-like cell death at 120 h after treatment. Moreover, transient combined treatment with H2 + Pt-nc induced cell-cycle arrest, as reflected by decreased proportions of G1-phase cells and accumulation of G2/M-phase cells. In contrast, intracellular peroxide levels were temporarily and significantly increased immediately after H2 + Pt-nc treatment but not after treatment with H2 or Pt-nc alone. Additionally, combined treatment-induced carcinostatic effects were significantly diminished in the presence of catalase, and marked hydrogen peroxide (H2O2) generation was confirmed after mixing Pt-nc into cell culture media containing a high concentration of H2. These changes are in agreement with the results that carcinostatic effects were induced after only 40 min of treatment with H2 + Pt-nc. Thus, transient and marked generation of H2O2 is responsible for the carcinostatic effects of combined treatment with H2 + Pt-nc.
authors.affiliation: a Laboratory of Bioscience & Biotechnology for Cell Function Control , Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima , Shobara , Hiroshima , Japan ;
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Saitoh
authors.affiliation: a Laboratory of Bioscience & Biotechnology for Cell Function Control , Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima , Shobara , Hiroshima , Japan ;
authors.forename: Minoru
authors.initials: M
authors.lastname: Ikeshima
authors.affiliation: a Laboratory of Bioscience & Biotechnology for Cell Function Control , Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima , Shobara , Hiroshima , Japan ;
authors.forename: Naho
authors.initials: N
authors.lastname: Kawasaki
authors.affiliation: a Laboratory of Bioscience & Biotechnology for Cell Function Control , Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima , Shobara , Hiroshima , Japan ;
authors.forename: Aoi
authors.initials: A
authors.lastname: Masumoto
authors.affiliation: b Department of Radiological Technology, Faculty of Health Sciences , Butsuryo College of Osaka , Sakai , Osaka , Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Miwa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002374:Catalase / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003102:Colloids; D054697:Cytostatic Agents / Q000494:pharmacology*; D053837:DNA Cleavage / Q000187:drug effects; D004338:Drug Combinations; D004357:Drug Synergism; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006859:Hydrogen / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000819:agonists* / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D049329:Nanostructures; D010984:Platinum / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D003102:Colloids; D054697:Cytostatic Agents; D004338:Drug Combinations; D010984:Platinum; D006859:Hydrogen; D006861:Hydrogen Peroxide; D002374:Catalase
keywords: Ehrlich ascites tumor cells; growth arrest; hydrogen-dissolved solution; nanomedicine; oxidative stress