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Antitumor Activity of Protons and Molecular Hydrogen: Mechanisms

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Antitumor Activity of Protons and Molecular Hydrogen: Mechanisms ( antitumor-activity-protons-and-molecular-hydrogen-mechanisms )

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cancers Review Antitumor Activity of Protons and Molecular Hydrogen: Underlying Mechanisms Luc Rochette 1,*, Marianne Zeller 1 , Yves Cottin 1,2 and Catherine Vergely 1 􏰁􏰂􏰃 􏰅􏰆􏰇 􏰈􏰉􏰊􏰋􏰌􏰂􏰍 Citation: Rochette,L.;Zeller,M.; Cottin, Y.; Vergely, C. Antitumor Activity of Protons and Molecular Hydrogen: Underlying Mechanisms. Cancers 2021, 13, 893. https:// doi.org/10.3390/cancers13040893 Academic Editors: Manish S. Patankar and Alexandros G. Georgakilas Received: 4 December 2020 Accepted: 16 February 2021 Published: 20 February 2021 Abstract: Understanding the structure and dynamics of the various hydrogen forms has been a subject of numerous studies. Protons (H+) and molecular hydrogen (H ) in the cell are critical in a 1 PEC2 (EA7460), Faculty of Health Sciences, University Bourgogne-Franche Comte, 7 Bd Jeanne d’Arc, 21000 Dijon, France; marianne.zeller@u-bourgogne.fr (M.Z.); yves.cottin@chu-dijon.fr (Y.C.); cvergely@u-bourgogne.fr (C.V.) Department of Cardiology, University Hospital of Dijon, 21000 Dijon, France 2 * Correspondence: luc.rochette@u-bourgogne.fr; Tel.: +33-380-393-291 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). small molecular weight, H2 can rapidly penetrate cell membranes and reach subcellular components to protect nuclear DNA and mitochondria. H2 reduces oxidative stress, exerts anti-inflammatory effects, and acts as a modulator of apoptosis. Exogenous H2, administered by inhalation, drinking H2-rich water, or injecting H2-rich saline solution, is a protective therapy that can be used in multiple diseases, including cancer. In particle therapy, cyclotrons and synchrotrons are the accelerators currently used to produce protons. Proton beam radiotherapy (PBT) offers great promise for the treatment of a wide variety of cancers due to the sharp decrease in the dose of radiation at a defined point. In these conditions, H2 and different types of H2 donors may represent a novel therapeutic strategy in cancer treatment. Keywords: molecular hydrogen; antioxidant; cancer 1. Introduction Oxidation and reduction are ubiquitous reactions that play key roles in the chemistry of aerobic organisms. Disturbances in the cellular redox balance have been related to pro-aging mechanisms and an increased risk of diseases such as cancers. A shift in the balance between oxidants and antioxidants in favor of oxidants is known as “oxidative stress”. Oxidative stress (OS) is a deviation from the steady redox state, and it indicates an imbalance due to excess levels of reactive oxygen species (ROS) or oxidants that surpass the cell’s capability to provide an efficient antioxidant response [1]. The dysregulation of cellular pH is a well-known characteristic of malignancy. Both hydrogen transport and cytoplasmic pH play critical roles in the management of cell growth and proliferation, and tumorigenesis. In the cell, protons (H+) and molecular hydrogen (H2) are critical in a wide variety of processes. Recently, H2 has been studied in preclinical and clinical trials on various diseases associated with oxidative and inflammatory stress. In this context, there has been much interest in H2 and H+ as possible therapeutic approaches in cancer. Simple Summary: Protons (H+) and molecular hydrogen (H2) in the cell are critical in a wide variety of processes. New cancer treatment uses H2, a biologically inactive gas. H2 can rapidly penetrate cell membranes and reach subcellular components to protect nuclear DNA and mitochondria. H2 reduces oxidative stress, exerts anti-inflammatory effects, and acts as a modulator of apoptosis. Exogenous H2 is a protective therapy that can be used in cancer. Cyclotrons and synchrotrons are currently used to produce protons. Proton beam radiotherapy (PBT) offers great promise for the treatment of a wide variety of cancers. H2 and different types of H2 donors may represent a novel therapeutic strategy in cancer treatment. 2 wide variety of processes. A new cancer treatment uses H2, a biologically inactive gas. Due to its Cancers 2021, 13, 893. https://doi.org/10.3390/cancers13040893 https://www.mdpi.com/journal/cancers

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