Hydrogen-bubbled platinum-colloid suppresses human esophagus- or tongue-carcinoma cells with intracellular platinum-upta

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RESEARCH ARTICLE

Hydrogen‑bubbled platinum‑colloid suppresses human esophagus‑ or tongue‑carcinoma cells with intracellular platinum‑uptake and the diminished normal‑cell mortality Shinya Kato1 · Yasukazu Saitoh2 · Nobuhiko Miwa3 Received: 7 June 2020 / Accepted: 15 July 2020 © Japan Human Cell Society 2020

Abstract Carcinostatic effects of combined use of hydrogen nano-bubbles (nano-H) and platinum–povidone (PVP-–Pt) were examined. Hydrogen-dissolved medium was prepared by hydrogen-gas bubbling with a microporous gas-emittance-terminal into a medium in the absence or presence of PVP–Pt (nano-H, nano-H/PVP–Pt). Human esophagus-derived carcinoma cells KYSE70 were repressed for cell proliferation with nano-H/PVP–Pt more markedly than with nano-H, indicating the hydrogen-intensification for PVP–Pt-alone-carcinostasis. However, the intensified carcinostasis required co-administration of nano-H and PVP–Pt, and no intensified carcinostasis was shown in two-step separate administration of nano-H and PVP–Pt. Furthermore, hydrogen bubbling into PVP–Pt-containing medium achieved more appreciable carcinostasis than mere addition of PVP–Pt into nano-H-containing medium, indicating the potent interaction of hydrogen and PVP–Pt. The nano-H/ PVP–Pt-administered human tongue-derived carcinoma cells HSC-4 were repressed for cell proliferation more markedly than pre-malignant human tongue-derived epitheliocytes DOK, concurrently with more abundant intracellular Pt-intake into HSC-4 cells than DOK as analyzed by ICP-MS. Thus, PVP–Pt is able to adsorb hydrogen nano-bubbles on Pt and applicable for cancer therapy by diminishing the side-effects to normal cells. Keywords  Hydrogen nano-bubbles · Platinum colloid · Human esophageal squamous carcinoma cells · Cell proliferation degree · Human tongue-derived carcinoma cells

Introduction Recently, hydrogen has been often studied for medical applications due to its antioxidant activity in the form of hydrogen-dissolved water, and various hydrogen waters are commercially available [1]. However, there is a problem that hydrogen has a low solubility in water (max. approximately 1.62 mg/L for room temperatures and atmosphere * Shinya Kato kato‑[email protected]‑u.ac.jp 1



Radioisotope Facilities for Medical Science, Advanced Science Research Promotion Center, Mie University, Edobashi 2‑174, Tsu, Mie 514‑8507, Japan

2



Laboratory of Bioscience and Biotechnology for Cell Function Control, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Nanatsuka 5562, Shobara, Hiroshima 727‑0023, Japan

3

Prefectural University of Hiroshima, Nanatsuka 5562, Shobara, Hiroshima 727‑0023, Japan



pressures) and is easily released from a beverage bottle because hydrogen molecule (­ H2) is small and permeable. Platinum colloids are known to have a high catalytic ability [2], and atomic hydrogen is therefore easy to be adsorbed on platinum surfaces [3,4]. We found that reactive oxygen species (ROS)-scavenging ability of H ­ 2 was improved in combination with platinum coll