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Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1
PURPOSE: Radiotherapy (RT) is one of main strategies of cancer treatment. However, some cancer cells are resistant to radiation-induced cell death, including apoptosis. Therefore, alternative approaches targeting different anti-tumor mechanisms such as cell senescence are required. This study aimed...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Cancer Association
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291200/ https://www.ncbi.nlm.nih.gov/pubmed/33321563 http://dx.doi.org/10.4143/crt.2020.1015 |
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author | Choi, Hoon Sik Kim, Jin Hyun Jang, Si Jung Yun, Jeong Won Kang, Ki Mun Jeong, Hojin Ha, In Bong Jeong, Bae Kwon |
author_facet | Choi, Hoon Sik Kim, Jin Hyun Jang, Si Jung Yun, Jeong Won Kang, Ki Mun Jeong, Hojin Ha, In Bong Jeong, Bae Kwon |
author_sort | Choi, Hoon Sik |
collection | PubMed |
description | PURPOSE: Radiotherapy (RT) is one of main strategies of cancer treatment. However, some cancer cells are resistant to radiation-induced cell death, including apoptosis. Therefore, alternative approaches targeting different anti-tumor mechanisms such as cell senescence are required. This study aimed to investigate the synergistic effect of alpha-lipoic acid (ALA) on radiation-induced cell death and senescence in MDA-MB-231 human breast cancer cells. MATERIALS AND METHODS: The cells were divided into four groups depending on the cell treatment (control, ALA, RT, and ALA+RT). Cells were analyzed for morphology, apoptotic cell death, mitochondrial reactive oxygen species, membrane potential, cellular senescence, and cell cycle. RESULTS: Our data showed that ALA significantly promoted apoptotic cell death when combined with RT, as reflected by Annexin V staining, expression of apoptosis-related factors, mitochondrial damages as well as cell morphological changes and reduction of cell numbers. In addition, ALA significantly enhanced radiation-induced cellular senescence, which was shown by increased HMGB1 expression in the cytosol fraction compared to the control, increased p53 expression compared to the control, activation of p38 as well as nuclear factor κB, and G2/M cell cycle arrest. CONCLUSION: The current study is the first report showing a new mode of action (senescence induction) of ALA beyond apoptotic cell death in MDA-MB-231 cancer cells known to be resistant to RT. |
format | Online Article Text |
id | pubmed-8291200 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Korean Cancer Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-82912002021-08-04 Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1 Choi, Hoon Sik Kim, Jin Hyun Jang, Si Jung Yun, Jeong Won Kang, Ki Mun Jeong, Hojin Ha, In Bong Jeong, Bae Kwon Cancer Res Treat Original Article PURPOSE: Radiotherapy (RT) is one of main strategies of cancer treatment. However, some cancer cells are resistant to radiation-induced cell death, including apoptosis. Therefore, alternative approaches targeting different anti-tumor mechanisms such as cell senescence are required. This study aimed to investigate the synergistic effect of alpha-lipoic acid (ALA) on radiation-induced cell death and senescence in MDA-MB-231 human breast cancer cells. MATERIALS AND METHODS: The cells were divided into four groups depending on the cell treatment (control, ALA, RT, and ALA+RT). Cells were analyzed for morphology, apoptotic cell death, mitochondrial reactive oxygen species, membrane potential, cellular senescence, and cell cycle. RESULTS: Our data showed that ALA significantly promoted apoptotic cell death when combined with RT, as reflected by Annexin V staining, expression of apoptosis-related factors, mitochondrial damages as well as cell morphological changes and reduction of cell numbers. In addition, ALA significantly enhanced radiation-induced cellular senescence, which was shown by increased HMGB1 expression in the cytosol fraction compared to the control, increased p53 expression compared to the control, activation of p38 as well as nuclear factor κB, and G2/M cell cycle arrest. CONCLUSION: The current study is the first report showing a new mode of action (senescence induction) of ALA beyond apoptotic cell death in MDA-MB-231 cancer cells known to be resistant to RT. Korean Cancer Association 2021-07 2020-12-15 /pmc/articles/PMC8291200/ /pubmed/33321563 http://dx.doi.org/10.4143/crt.2020.1015 Text en Copyright © 2021 by the Korean Cancer Association https://creativecommons.org/licenses/by-nc/4.0/This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Choi, Hoon Sik Kim, Jin Hyun Jang, Si Jung Yun, Jeong Won Kang, Ki Mun Jeong, Hojin Ha, In Bong Jeong, Bae Kwon Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1 |
title | Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1 |
title_full | Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1 |
title_fullStr | Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1 |
title_full_unstemmed | Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1 |
title_short | Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1 |
title_sort | synergistic tumoricidal effects of alpha-lipoic acid and radiotherapy on human breast cancer cells via hmgb1 |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291200/ https://www.ncbi.nlm.nih.gov/pubmed/33321563 http://dx.doi.org/10.4143/crt.2020.1015 |
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