ON01210.Na (Ex-RAD®) mitigates radiation damage through activation of the AKT pathway

• Published in: PloS one Vol. 8; no. 3; p. e58355
• Main Authors: Kang, Anthony D, Cosenza, Stephen C, Bonagura, Marie, Manair, Manoj, Reddy, M V Ramana, Reddy, E Premkumar
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07-03-2013; Public Library of Science (PLoS)
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Animals; Apoptosis; Biocompatibility; Biology; Bone marrow; Bone Marrow Cells - drug effects; Bone Marrow Cells - radiation effects; Cancer therapies; Cell cycle; Cell Cycle - drug effects; Cell division; Cell Proliferation - drug effects; Cell Survival; Deoxyribonucleic acid; Disasters; DNA; DNA Damage - drug effects; DNA Damage - radiation effects; DNA repair; Drug dosages; Exposure; Fibroblasts; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - radiation effects; Hematopoietic system; Humans; Ionizing radiation; Medical research; Medical screening; Medicine; Mice; Molecular biology; Nuclear engineering; Proto-Oncogene Proteins c-akt - metabolism; Radiation; Radiation damage; Radiation dosage; Radiation effects; Radiation-Protective Agents - pharmacology; Signal Transduction - drug effects; Signal Transduction - radiation effects; Small Molecule Libraries; Space exploration; Stem cells; Sulfonamides - pharmacology; Terrorism; New York; United States > US; Pennsylvania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0058355

Development of radio-protective agents that are non-toxic is critical in light of ever increasing threats associated with proliferation of nuclear materials, terrorism and occupational risks associated with medical and space exploration. In this communication, we describe the discovery, characterization and mechanism of action of ON01210.Na, which effectively protects mouse and human bone marrow cells from radiation-induced damage both in vitro and in vivo. Our results show that treatment of normal fibroblasts with ON01210.Na before and after exposure to ionizing radiation provides dose dependent protection against radiation-induced damage. Treatment of mice with ON01210.Na prior to radiation exposure was found to result in a more rapid recovery of their hematopoietic system. The mechanistic studies described here show that ON01210.Na manifests its protective effects through the up-regulation of PI3-Kinase/AKT pathways in cells exposed to radiation. These results suggest that ON 01210.Na is a safe and effective radioprotectant and could be a novel agent for use in radiobiological disasters.