Synthetic Secoisolariciresinol Diglucoside (LGM2605) Protects Human Lung in an Ex Vivo Model of Proton Radiation Damage
Open accessAbstract
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.
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Lignans protect tissues and organs against oxidative stress, inflammation, and senescence by acting as neuroprotective and radioprotective agents.
“Moreover, lignans molecules can protect tissues and organs against OS, inflammation, and senescence by acting as neuroprotective and radioprotective agents [405,406].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [406]
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Cites
The first 30 years of p53: growing ever more complex.
Levine, A. J., & Oren, M. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2723 · Cited by 1,967 · see citing works
Cytoplasmic functions of the tumour suppressor p53
Green, D. R., & Kroemer, G. (2009) · Nature · doi:10.1038/nature07986 · Cited by 1,106 · see citing works
Space Radiation: The number one risk to astronaut health beyond low earth orbit
Chancellor, J., Scott, G., & Sutton, J. (2014) · Life · doi:10.3390/life4030491 · Cited by 455 · see citing works
Ionizing Radiation-Induced Endothelial Cell Senescence and Cardiovascular Diseases
Wang, Y., Boerma, M., & Zhou, D. (2016) · Radiation Research · doi:10.1667/rr14445.1 · Cited by 204 · see citing works
Fontenot, J. D., Lee, A. K., & Newhauser, W. D. (2009) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2009.01.001 · Cited by 150 · see citing works
Brodin, N. P., af Rosenschöld, P. M., Aznar, M. C., Kiil-Berthelsen, A., Vogelius, I. R., Nilsson, P. G., Lannering, B., & Björk‐Eriksson, T. (2011) · Acta Oncologica · doi:10.3109/0284186x.2011.582514 · Cited by 138 · see citing works
Lafargue, A., Degorre, C., Corre, I., Alves-Guerra, M.-C., Gaugler, M.-H., Vallette, F., Pecqueur, C., & Paris, F. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.04.019 · Cited by 131 · see citing works
Inflammation in lung carcinogenesis: New targets for lung cancer chemoprevention and treatment
Lee, J. M., Yanagawa, J., Peebles, K. A., Sharma, S. P., Mao, J. T., & Dubinett, S. M. (2008) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2008.01.004 · Cited by 120 · see citing works
Stressing the cell cycle in senescence and aging
Chandler, H., & Peters, G. (2013) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2013.07.005 · Cited by 119 · see citing works
Ciliary Beat Frequency Is Maintained at a Maximal Rate in the Small Airways of Mouse Lung Slices
Delmotte, P. F., & Sanderson, M. J. (2006) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2005-0417oc · Cited by 115 · see citing works
Lee, J. C., Krochak, R., Blouin, A., Kanterakis, S., Chatterjee, S., Arguiri, E., Vachani, A., Solomides, C., Cengel, K. A., & Christofidou‐Solomidou, M. (2009) · Cancer Biology & Therapy · doi:10.4161/cbt.8.1.7092 · Cited by 106 · see citing works
Self-citationCooper, P. R., Lamb, R. J., Day, N. D., Branigan, P. J., Kajekar, R., Mateo, L. S., Hornby, P. J., & Panettieri, R. A. (2009) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00133.2009 · Cited by 72 · see citing works
Self-citationTsuboi, K., Moritake, T., Tsuchida, Y., Tokuuye, K., Matsumura, A., & Andō, K. (2007) · Journal of Radiation Research · doi:10.1269/jrr.06081 · Cited by 65 · see citing works
New era of radiotherapy: An update in radiation-induced lung disease
Benveniste, M. F. K., Welsh, J. D., Godoy, M. C. B., Betancourt, S. L., Mawlawi, O. R., & Munden, R. F. (2013) · Clinical Radiology · doi:10.1016/j.crad.2013.01.013 · Cited by 64 · see citing works
Resveratrol enhances ionizing radiation-induced premature senescence in lung cancer cells
Luo, H., Wang, L., Schulte, B. A., Yang, A., Tang, S., & Wang, G. Y. (2013) · International Journal of Oncology · doi:10.3892/ijo.2013.2141 · Cited by 64 · see citing works
MiR-34a modulates ionizing radiation-induced senescence in lung cancer cells
He, X., Yang, A., McDonald, D. G., Riemer, E. C., Vanek, K. N., Schulte, B. A., & Wang, G. Y. (2017) · Oncotarget · doi:10.18632/oncotarget.19267 · Cited by 64 · see citing works
Velalopoulou, A. P., Tyagi, S., Pietrofesa, R. A., Arguiri, E., & Christofidou‐Solomidou, M. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms17010007 · Cited by 62 · see citing works
Self-citationPietrofesa, R. A., Velalopoulou, A. P., Albelda, S. Μ., & Christofidou‐Solomidou, M. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17030322 · Cited by 58 · see citing works
Self-citationProspective study of proton‐beam radiation therapy for limited‐stage small cell lung cancer
Rwigema, J. M., Verma, V., Lin, L., Berman, A. T., Levin, W. P., Evans, T. L., Aggarwal, C., Rengan, R., Langer, C. J., Cohen, R. B., et al. (2017) · Cancer · doi:10.1002/cncr.30870 · Cited by 58 · see citing works
Self-citationPietrofesa, R. A., Velalopoulou, A. P., Arguiri, E., Menges, C. W., Testa, J. R., Hwang, W., Albelda, S. Μ., & Christofidou‐Solomidou, M. (2015) · Carcinogenesis · doi:10.1093/carcin/bgv174 · Cited by 56 · see citing works
Self-citationRadiation mitigating properties of the lignan component in flaxseed
Pietrofesa, R. A., Turowski, J. B., Tyagi, S., Dukes, F., Arguiri, E., Busch, T. M., Gallagher‐Colombo, S. M., Solomides, C., Cengel, K. A., & Christofidou‐Solomidou, M. (2013) · BMC Cancer · doi:10.1186/1471-2407-13-179 · Cited by 53 · see citing works
Self-citationChristofidou‐Solomidou, M., Tyagi, S., Tan, K.-S., Hagan, S., Pietrofesa, R. A., Dukes, F., Arguiri, E., Heitjan, D. F., Solomides, C., & Cengel, K. A. (2011) · BMC Cancer · doi:10.1186/1471-2407-11-269 · Cited by 52 · see citing works
Self-citationBerman, A. T., Teo, B.-K. K., Dolney, D., Swisher-McClure, S. D., Shahnazi, K., Both, S., & Rengan, R. (2013) · Radiation Oncology · doi:10.1186/1748-717x-8-144 · Cited by 49 · see citing works
Self-citationChristofidou‐Solomidou, M., Tyagi, S., Pietrofesa, R. A., Dukes, F., Arguiri, E., Turowski, J. B., Grieshaber, P. A., Solomides, C., & Cengel, K. A. (2012) · Radiation Research · doi:10.1667/rr2980.1 · Cited by 44 · see citing works
Self-citationRemick, J. S., Schonewolf, C. A., Gabriel, P. E., Doucette, A. G., Levin, W. P., Kucharczuk, J. C., Singhal, S. K., Pechet, T. T. V., Rengan, R., Simone, C. B., et al. (2017) · Clinical Lung Cancer · doi:10.1016/j.cllc.2016.12.009 · Cited by 42 · see citing works
Self-citationSpace radiation-associated lung injury in a murine model
Christofidou‐Solomidou, M., Pietrofesa, R. A., Arguiri, E., Schweitzer, K. S., Berdyshev, E. V., McCarthy, M. P., Corbitt, A., Alwood, J. S., Yu, Y., Globus, R. K., et al. (2014) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00260.2014 · Cited by 41 · see citing works
Self-citationRosenzweig, K. E., & Gomez, J. E. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.69.9678 · Cited by 39 · see citing works
Biological Characterization of Low-Energy Ions with High-Energy Deposition on Human Cells
Saha, J., Wilson, P., Thieberger, P., Lowenstein, D. I., Wang, M., & Cucinotta, F. A. (2014) · Radiation Research · doi:10.1667/rr13747.1 · Cited by 35 · see citing works
Proton Radiotherapy for Solid Tumors of Childhood
Cotter, S. E., McBride, S. M., & Yock, T. I. (2012) · Technology in Cancer Research & Treatment · doi:10.7785/tcrt.2012.500295 · Cited by 33 · see citing works
Synthesis and antioxidant evaluation of (S,S)- and (R,R)-secoisolariciresinol diglucosides (SDGs)
Mishra, O. P., Simmons, N., Tyagi, S., Pietrofesa, R. A., Shuvaev, V. V., Valiulin, R. A., Heretsch, P. M., Nicolaou, K. C., & Christofidou‐Solomidou, M. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.07.062 · Cited by 32 · see citing works
Self-citationKoziol‐White, C. J., Jia, Y., Baltus, G. A., Cooper, P. R., Zaller, D. M., Crackower, M. A., Sirkowski, E. E., Smock, S. L., Northrup, A. B., Himes, B. E., et al. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13550 · Cited by 26 · see citing works
Self-citationMishra, O. P., Pietrofesa, R. A., & Christofidou‐Solomidou, M. (2014) · Radiation Research · doi:10.1667/rr13635.1 · Cited by 21 · see citing works
Self-citationBS, J. B. T. E. A. (2013) · Journal of Pulmonary & Respiratory Medicine · doi:10.4172/2161-105x.1000158 · Cited by 15 · see citing works
Pietrofesa, R., Velalopoulou, A., Lehman, S., Arguiri, E., Solomides, P., Koch, C., Mishra, O., Koumenis, C., Goodwin, T., & Christofidou-Solomidou, M. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17060953 · Cited by 13 · see citing works
Self-citationFeliciano, J. L., Feigenberg, S. J., & Mehta, M. P. (2013) · The Cancer Journal · doi:10.1097/ppo.0b013e318293238d · Cited by 10 · see citing works
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- Authors
- Velalopoulou, A., Chatterjee, S., Pietrofesa, R., Koziol-White, C., Panettieri, R., Lin, L., Tuttle, S., Berman, A., Koumenis, C., & Christofidou-Solomidou, M.
- Affiliations
- University of Pennsylvania (US)
- Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Pennsylvania Perelman School of Medicine, 3450 Hamilton Walk, Stemmler Hall, Office Suite 227, Philadelphia, PA 19104, USA
- ORCID
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2017-11-25
- Volume
- 18
- Issue
- 12
- Pages
- 2525
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC5751128
- OpenAlex
- W2769972663
- Cited by
- 22
- References
- 35
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 6 · 2020: 1 · 2019: 3 · 2018: 3
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (NIH-R01 CA133470, NIH-1R21CA178654-01, NIH-1R21NS087406-01, NIH-R03 CA180548, 1P42ES023720-01, 1P30 ES013508-02)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiation Dose and Imaging
- Keywords
- secoisolariciresinol diglucoside, proton radiation, radiation-induced lung injury, radiation protection, precision-cut lung slices, cellular senescence, oxidative stress, inflammation, cell cycle arrest, space radiation, thoracic radiotherapy
- MeSH terms
- Anti-Inflammatory Agents, Butylene Glycols, Glucosides, Humans, Lung, Protons, Radiation-Protective Agents, Cellular Senescence, Radiation Pneumonitis, Oxidative Stress, Cell Cycle Checkpoints
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