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Butyrate reverses ferroptosis resistance in colorectal cancer by inducing c-Fos-dependent xCT suppression
Ferroptosis has emerged to be a promising approach in cancer therapies; however, colorectal cancer (CRC) is relatively insensitive to ferroptosis. Exactly how the gut microenvironment impacts the ferroptotic sensitivity of CRC remains unknown. Herein, by performing metabolomics, we discovered that b...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10388208/ https://www.ncbi.nlm.nih.gov/pubmed/37494767 http://dx.doi.org/10.1016/j.redox.2023.102822 |
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author | He, Ying Ling, Yuhang Zhang, Zhiyong Mertens, Randall Tyler Cao, Qian Xu, Xutao Guo, Ke Shi, Qian Zhang, Xilin Huo, Lixia Wang, Kan Guo, Huihui Shen, Weiyun Shen, Manlu Feng, Wenming Xiao, Peng |
author_facet | He, Ying Ling, Yuhang Zhang, Zhiyong Mertens, Randall Tyler Cao, Qian Xu, Xutao Guo, Ke Shi, Qian Zhang, Xilin Huo, Lixia Wang, Kan Guo, Huihui Shen, Weiyun Shen, Manlu Feng, Wenming Xiao, Peng |
author_sort | He, Ying |
collection | PubMed |
description | Ferroptosis has emerged to be a promising approach in cancer therapies; however, colorectal cancer (CRC) is relatively insensitive to ferroptosis. Exactly how the gut microenvironment impacts the ferroptotic sensitivity of CRC remains unknown. Herein, by performing metabolomics, we discovered that butyrate concentrations were significantly decreased in CRC patients. Butyrate supplementation sensitized CRC mice to ferroptosis induction, showing great in vivo translatability. Particularly, butyrate treatment reduced ferroptotic resistance of cancer stem cells. Mechanistically, butyrate inhibited xCT expression and xCT-dependent glutathione synthesis. Moreover, we identified c-Fos as a novel xCT suppressor, and further elucidated that butyrate induced c-Fos expression via disrupting class I HDAC activity. In CRC patients, butyrate negatively correlated with tumor xCT expression and positively correlated with c-Fos expression. Finally, butyrate was found to boost the pro-ferroptotic function of oxaliplatin (OXA). Immunohistochemistry data showed that OXA non-responders exhibited higher xCT expression compared to OXA responders. Hence, butyrate supplementation is a promising approach to break the ferroptosis resistance in CRC. |
format | Online Article Text |
id | pubmed-10388208 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-103882082023-08-01 Butyrate reverses ferroptosis resistance in colorectal cancer by inducing c-Fos-dependent xCT suppression He, Ying Ling, Yuhang Zhang, Zhiyong Mertens, Randall Tyler Cao, Qian Xu, Xutao Guo, Ke Shi, Qian Zhang, Xilin Huo, Lixia Wang, Kan Guo, Huihui Shen, Weiyun Shen, Manlu Feng, Wenming Xiao, Peng Redox Biol Research Paper Ferroptosis has emerged to be a promising approach in cancer therapies; however, colorectal cancer (CRC) is relatively insensitive to ferroptosis. Exactly how the gut microenvironment impacts the ferroptotic sensitivity of CRC remains unknown. Herein, by performing metabolomics, we discovered that butyrate concentrations were significantly decreased in CRC patients. Butyrate supplementation sensitized CRC mice to ferroptosis induction, showing great in vivo translatability. Particularly, butyrate treatment reduced ferroptotic resistance of cancer stem cells. Mechanistically, butyrate inhibited xCT expression and xCT-dependent glutathione synthesis. Moreover, we identified c-Fos as a novel xCT suppressor, and further elucidated that butyrate induced c-Fos expression via disrupting class I HDAC activity. In CRC patients, butyrate negatively correlated with tumor xCT expression and positively correlated with c-Fos expression. Finally, butyrate was found to boost the pro-ferroptotic function of oxaliplatin (OXA). Immunohistochemistry data showed that OXA non-responders exhibited higher xCT expression compared to OXA responders. Hence, butyrate supplementation is a promising approach to break the ferroptosis resistance in CRC. Elsevier 2023-07-20 /pmc/articles/PMC10388208/ /pubmed/37494767 http://dx.doi.org/10.1016/j.redox.2023.102822 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Paper He, Ying Ling, Yuhang Zhang, Zhiyong Mertens, Randall Tyler Cao, Qian Xu, Xutao Guo, Ke Shi, Qian Zhang, Xilin Huo, Lixia Wang, Kan Guo, Huihui Shen, Weiyun Shen, Manlu Feng, Wenming Xiao, Peng Butyrate reverses ferroptosis resistance in colorectal cancer by inducing c-Fos-dependent xCT suppression |
title | Butyrate reverses ferroptosis resistance in colorectal cancer by inducing c-Fos-dependent xCT suppression |
title_full | Butyrate reverses ferroptosis resistance in colorectal cancer by inducing c-Fos-dependent xCT suppression |
title_fullStr | Butyrate reverses ferroptosis resistance in colorectal cancer by inducing c-Fos-dependent xCT suppression |
title_full_unstemmed | Butyrate reverses ferroptosis resistance in colorectal cancer by inducing c-Fos-dependent xCT suppression |
title_short | Butyrate reverses ferroptosis resistance in colorectal cancer by inducing c-Fos-dependent xCT suppression |
title_sort | butyrate reverses ferroptosis resistance in colorectal cancer by inducing c-fos-dependent xct suppression |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10388208/ https://www.ncbi.nlm.nih.gov/pubmed/37494767 http://dx.doi.org/10.1016/j.redox.2023.102822 |
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