Synthetic secoisolariciresinol diglucoside (LGM2605) protects human lung in an ex vivo model of proton radiation damage

• Authors: Anastasia Velalopoulou, University of Pennsylvania; Shampa Chatterjee, University of Pennsylvania; Ralph A. Pietrofesa, University of Pennsylvania; Cynthia Koziol-White, University of Pennsylvania; Reynold A. Panettieri, University of Pennsylvania; Liyong Lin, Emory University; Stephen Tuttle, University of Pennsylvania; Abigail Berman, University of Pennsylvania; Constantinos Koumenis, University of Pennsylvania; Melpo Christofidou-Solomidou, University of Pennsylvania
• Journal Title: International Journal of Molecular Sciences
• Volume: Volume 18, Number 12
• Publisher: MDPI | 2017-12-01, Pages 2525-2525
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.3390/ijms18122525
• Subjects: Health Sciences, Oncology; Health Sciences, Radiology
• Keywords: LGM2605; antioxidant; cell cycle; human lung sections; inflammation; organ culture; oxidative stress; phase II enzymes; proton radiation; reactive oxygen species; senescence; Anti-Inflammatory Agents; Butylene Glycols; Cell Cycle Checkpoints; Cellular Senescence; Glucosides; Humans; Lung; Oxidative Stress; Protons; Radiation Pneumonitis; Radiation-Protective Agents

Abstract

Radiation therapy for the treatment of thoracic malignancies has improved significantly by directing of the proton beam in higher doses on the targeted tumor while normal tissues around the tumor receive much lower doses. Nevertheless, exposure of normal tissues to protons is known to pose a substantial risk in long-term survivors, as confirmed by our work in space-relevant exposures of murine lungs to proton radiation. Thus, radioprotective strategies are being sought. We established that LGM2605 is a potent protector from radiation-induced lung toxicity and aimed in the current study to extend the initial findings of space-relevant, proton radiation-associated late lung damage in mice by looking at acute changes in human lung. We used an ex vivo model of organ culture where tissue slices of donor living human lung were kept in culture and exposed to proton radiation. We exposed donor human lung precision-cut lung sections (huPCLS), pretreated with LGM2605, to 4 Gy proton radiation and evaluated them 30 min and 24 h later for gene expression changes relevant to inflammation, oxidative stress, and cell cycle arrest, and determined radiation-induced senescence, inflammation, and oxidative tissue damage. We identified an LGM2605-mediated reduction of proton radiation-induced cellular senescence and associated cell cycle changes, an associated proinflammatory phenotype, and associated oxidative tissue damage. This is a first report on the effects of proton radiation and of the radioprotective properties of LGM2605 on human lung.