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Bacterial diet modulates tamoxifen-induced death via host fatty acid metabolism

Tamoxifen is a selective estrogen receptor (ER) modulator that is used to treat ER-positive breast cancer, but that at high doses kills both ER-positive and ER-negative breast cancer cells. We recapitulate this off-target effect in Caenorhabditis elegans, which does not have an ER ortholog. We find...

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Autores principales: Diot, Cédric, García-González, Aurian P., Vieira, Andre F., Walker, Melissa, Honeywell, Megan, Doyle, Hailey, Ponomarova, Olga, Rivera, Yomari, Na, Huimin, Zhang, Hefei, Lee, Michael, Olsen, Carissa P., Walhout, Albertha J. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508336/
https://www.ncbi.nlm.nih.gov/pubmed/36151093
http://dx.doi.org/10.1038/s41467-022-33299-5
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author Diot, Cédric
García-González, Aurian P.
Vieira, Andre F.
Walker, Melissa
Honeywell, Megan
Doyle, Hailey
Ponomarova, Olga
Rivera, Yomari
Na, Huimin
Zhang, Hefei
Lee, Michael
Olsen, Carissa P.
Walhout, Albertha J. M.
author_facet Diot, Cédric
García-González, Aurian P.
Vieira, Andre F.
Walker, Melissa
Honeywell, Megan
Doyle, Hailey
Ponomarova, Olga
Rivera, Yomari
Na, Huimin
Zhang, Hefei
Lee, Michael
Olsen, Carissa P.
Walhout, Albertha J. M.
author_sort Diot, Cédric
collection PubMed
description Tamoxifen is a selective estrogen receptor (ER) modulator that is used to treat ER-positive breast cancer, but that at high doses kills both ER-positive and ER-negative breast cancer cells. We recapitulate this off-target effect in Caenorhabditis elegans, which does not have an ER ortholog. We find that different bacteria dramatically modulate tamoxifen toxicity in C. elegans, with a three-order of magnitude difference between animals fed Escherichia coli, Comamonas aquatica, and Bacillus subtilis. Remarkably, host fatty acid (FA) biosynthesis mitigates tamoxifen toxicity, and different bacteria provide the animal with different FAs, resulting in distinct FA profiles. Surprisingly these bacteria modulate tamoxifen toxicity by different death mechanisms, some of which are modulated by FA supplementation and others by antioxidants. Together, this work reveals a complex interplay between microbiota, FA metabolism and tamoxifen toxicity that may provide a blueprint for similar studies in more complex mammals.
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spelling pubmed-95083362022-09-25 Bacterial diet modulates tamoxifen-induced death via host fatty acid metabolism Diot, Cédric García-González, Aurian P. Vieira, Andre F. Walker, Melissa Honeywell, Megan Doyle, Hailey Ponomarova, Olga Rivera, Yomari Na, Huimin Zhang, Hefei Lee, Michael Olsen, Carissa P. Walhout, Albertha J. M. Nat Commun Article Tamoxifen is a selective estrogen receptor (ER) modulator that is used to treat ER-positive breast cancer, but that at high doses kills both ER-positive and ER-negative breast cancer cells. We recapitulate this off-target effect in Caenorhabditis elegans, which does not have an ER ortholog. We find that different bacteria dramatically modulate tamoxifen toxicity in C. elegans, with a three-order of magnitude difference between animals fed Escherichia coli, Comamonas aquatica, and Bacillus subtilis. Remarkably, host fatty acid (FA) biosynthesis mitigates tamoxifen toxicity, and different bacteria provide the animal with different FAs, resulting in distinct FA profiles. Surprisingly these bacteria modulate tamoxifen toxicity by different death mechanisms, some of which are modulated by FA supplementation and others by antioxidants. Together, this work reveals a complex interplay between microbiota, FA metabolism and tamoxifen toxicity that may provide a blueprint for similar studies in more complex mammals. Nature Publishing Group UK 2022-09-23 /pmc/articles/PMC9508336/ /pubmed/36151093 http://dx.doi.org/10.1038/s41467-022-33299-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Diot, Cédric
García-González, Aurian P.
Vieira, Andre F.
Walker, Melissa
Honeywell, Megan
Doyle, Hailey
Ponomarova, Olga
Rivera, Yomari
Na, Huimin
Zhang, Hefei
Lee, Michael
Olsen, Carissa P.
Walhout, Albertha J. M.
Bacterial diet modulates tamoxifen-induced death via host fatty acid metabolism
title Bacterial diet modulates tamoxifen-induced death via host fatty acid metabolism
title_full Bacterial diet modulates tamoxifen-induced death via host fatty acid metabolism
title_fullStr Bacterial diet modulates tamoxifen-induced death via host fatty acid metabolism
title_full_unstemmed Bacterial diet modulates tamoxifen-induced death via host fatty acid metabolism
title_short Bacterial diet modulates tamoxifen-induced death via host fatty acid metabolism
title_sort bacterial diet modulates tamoxifen-induced death via host fatty acid metabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9508336/
https://www.ncbi.nlm.nih.gov/pubmed/36151093
http://dx.doi.org/10.1038/s41467-022-33299-5
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