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Radio-selective effects of a natural occurring muscle-derived dipeptide in A549 and normal cell lines

Radiotherapy (RT) causes morbidity and long-term side effects. A challenge in RT is to maximize cancer cells killing while minimizing damage to normal tissue. The ideal radio-protector selectively improves survival and limits damage to normal tissues while reducing survival of cancer cells. Muscle-d...

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Autores principales: Ybarra, Norma, Seuntjens, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687720/
https://www.ncbi.nlm.nih.gov/pubmed/31395939
http://dx.doi.org/10.1038/s41598-019-47944-5
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author Ybarra, Norma
Seuntjens, Jan
author_facet Ybarra, Norma
Seuntjens, Jan
author_sort Ybarra, Norma
collection PubMed
description Radiotherapy (RT) causes morbidity and long-term side effects. A challenge in RT is to maximize cancer cells killing while minimizing damage to normal tissue. The ideal radio-protector selectively improves survival and limits damage to normal tissues while reducing survival of cancer cells. Muscle-derived dipeptide, L-carnosine (CAR) is a potent antioxidant, with radio-protective, but also anticancer properties, affecting the cell cycle of cancer cells. We tested CAR effects in lung cancer cells, differentiated and undifferentiated normal cells. We hypothesized that CAR antioxidant properties will confer protection to the two normal cell lines against RT, while preventing lung cancer cell proliferation, and that CAR may act as a radiosensitizer of lung cancer cells due to its effects on cell-cycle progression of cancer cells. Under the experimental conditions reported here, we found that CAR increased radio-sensitivity of lung (A549) cancer cells by increasing the percentage of cells in G2/M (radiosensitive) phase of cell cycle, it negatively affected their bioenergetics, therefore reduced their viability, and DNA-double strand break repair capacity. CAR had either no effect or reduced RT-induced damage in normal cells, depending on the cell type. CAR is a versatile natural occurring compound, that could improve RT-induced lung cancer cells killing, while reducing the damage to normal differentiated and undifferentiated cells.
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spelling pubmed-66877202019-08-13 Radio-selective effects of a natural occurring muscle-derived dipeptide in A549 and normal cell lines Ybarra, Norma Seuntjens, Jan Sci Rep Article Radiotherapy (RT) causes morbidity and long-term side effects. A challenge in RT is to maximize cancer cells killing while minimizing damage to normal tissue. The ideal radio-protector selectively improves survival and limits damage to normal tissues while reducing survival of cancer cells. Muscle-derived dipeptide, L-carnosine (CAR) is a potent antioxidant, with radio-protective, but also anticancer properties, affecting the cell cycle of cancer cells. We tested CAR effects in lung cancer cells, differentiated and undifferentiated normal cells. We hypothesized that CAR antioxidant properties will confer protection to the two normal cell lines against RT, while preventing lung cancer cell proliferation, and that CAR may act as a radiosensitizer of lung cancer cells due to its effects on cell-cycle progression of cancer cells. Under the experimental conditions reported here, we found that CAR increased radio-sensitivity of lung (A549) cancer cells by increasing the percentage of cells in G2/M (radiosensitive) phase of cell cycle, it negatively affected their bioenergetics, therefore reduced their viability, and DNA-double strand break repair capacity. CAR had either no effect or reduced RT-induced damage in normal cells, depending on the cell type. CAR is a versatile natural occurring compound, that could improve RT-induced lung cancer cells killing, while reducing the damage to normal differentiated and undifferentiated cells. Nature Publishing Group UK 2019-08-08 /pmc/articles/PMC6687720/ /pubmed/31395939 http://dx.doi.org/10.1038/s41598-019-47944-5 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ybarra, Norma
Seuntjens, Jan
Radio-selective effects of a natural occurring muscle-derived dipeptide in A549 and normal cell lines
title Radio-selective effects of a natural occurring muscle-derived dipeptide in A549 and normal cell lines
title_full Radio-selective effects of a natural occurring muscle-derived dipeptide in A549 and normal cell lines
title_fullStr Radio-selective effects of a natural occurring muscle-derived dipeptide in A549 and normal cell lines
title_full_unstemmed Radio-selective effects of a natural occurring muscle-derived dipeptide in A549 and normal cell lines
title_short Radio-selective effects of a natural occurring muscle-derived dipeptide in A549 and normal cell lines
title_sort radio-selective effects of a natural occurring muscle-derived dipeptide in a549 and normal cell lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687720/
https://www.ncbi.nlm.nih.gov/pubmed/31395939
http://dx.doi.org/10.1038/s41598-019-47944-5
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