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MitoQ Prevents Human Breast Cancer Recurrence and Lung Metastasis in Mice †

SIMPLE SUMMARY: Entry in the metastatic phase is often devastating for cancer patients. Metastases originate from metastatic progenitor cells that are selected in the primary tumor and which simultaneously possess several phenotypic capabilities, including migration, invasion, and clonogenicity. We...

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Autores principales: Capeloa, Tania, Krzystyniak, Joanna, Rodriguez, Amanda Canas, Payen, Valéry L., Zampieri, Luca X., Pranzini, Erica, Derouane, Françoise, Vazeille, Thibaut, Bouzin, Caroline, Duhoux, François P., Murphy, Michael P., Porporato, Paolo E., Sonveaux, Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946761/
https://www.ncbi.nlm.nih.gov/pubmed/35326639
http://dx.doi.org/10.3390/cancers14061488
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author Capeloa, Tania
Krzystyniak, Joanna
Rodriguez, Amanda Canas
Payen, Valéry L.
Zampieri, Luca X.
Pranzini, Erica
Derouane, Françoise
Vazeille, Thibaut
Bouzin, Caroline
Duhoux, François P.
Murphy, Michael P.
Porporato, Paolo E.
Sonveaux, Pierre
author_facet Capeloa, Tania
Krzystyniak, Joanna
Rodriguez, Amanda Canas
Payen, Valéry L.
Zampieri, Luca X.
Pranzini, Erica
Derouane, Françoise
Vazeille, Thibaut
Bouzin, Caroline
Duhoux, François P.
Murphy, Michael P.
Porporato, Paolo E.
Sonveaux, Pierre
author_sort Capeloa, Tania
collection PubMed
description SIMPLE SUMMARY: Entry in the metastatic phase is often devastating for cancer patients. Metastases originate from metastatic progenitor cells that are selected in the primary tumor and which simultaneously possess several phenotypic capabilities, including migration, invasion, and clonogenicity. We previously provided in vitro evidence that these features are collectively enforced by mitochondrial superoxide in a paradigm where mitochondria act as metabolic sensors of the tumor microenvironment and produce subcytotoxic levels of superoxide to prime metastatic progenitor cells. We also showed that these metastatic traits can be collectively countered by MitoQ, a mitochondria-targeted antioxidant that selectively deactivates mitochondrial superoxide. Here, we further establish that MitoQ prevents primary tumor recurrence after surgery, tumor take and metastasis as a whole, notably in a model of human breast cancer in mice. Since MitoQ already successfully passed Phase I clinical trials, our findings support the development of this drug as a preventive treatment against breast cancer metastasis. ABSTRACT: In oncology, the occurrence of distant metastases often marks the transition from curative to palliative care. Such outcome is highly predictable for breast cancer patients, even if tumors are detected early, and there is no specific treatment to prevent metastasis. Previous observations indicated that cancer cell mitochondria are bioenergetic sensors of the tumor microenvironment that produce superoxide to promote evasion. Here, we tested whether mitochondria-targeted antioxidant MitoQ is capable to prevent metastasis in the MDA-MB-231 model of triple-negative human breast cancer in mice and in the MMTV-PyMT model of spontaneously metastatic mouse breast cancer. At clinically relevant doses, we report that MitoQ not only prevented metastatic take and dissemination, but also local recurrence after surgery. We further provide in vitro evidence that MitoQ does not interfere with conventional chemotherapies used to treat breast cancer patients. Since MitoQ already successfully passed Phase I safety clinical trials, our preclinical data collectively provide a strong incentive to test this drug for the prevention of cancer dissemination and relapse in clinical trials with breast cancer patients.
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spelling pubmed-89467612022-03-25 MitoQ Prevents Human Breast Cancer Recurrence and Lung Metastasis in Mice † Capeloa, Tania Krzystyniak, Joanna Rodriguez, Amanda Canas Payen, Valéry L. Zampieri, Luca X. Pranzini, Erica Derouane, Françoise Vazeille, Thibaut Bouzin, Caroline Duhoux, François P. Murphy, Michael P. Porporato, Paolo E. Sonveaux, Pierre Cancers (Basel) Article SIMPLE SUMMARY: Entry in the metastatic phase is often devastating for cancer patients. Metastases originate from metastatic progenitor cells that are selected in the primary tumor and which simultaneously possess several phenotypic capabilities, including migration, invasion, and clonogenicity. We previously provided in vitro evidence that these features are collectively enforced by mitochondrial superoxide in a paradigm where mitochondria act as metabolic sensors of the tumor microenvironment and produce subcytotoxic levels of superoxide to prime metastatic progenitor cells. We also showed that these metastatic traits can be collectively countered by MitoQ, a mitochondria-targeted antioxidant that selectively deactivates mitochondrial superoxide. Here, we further establish that MitoQ prevents primary tumor recurrence after surgery, tumor take and metastasis as a whole, notably in a model of human breast cancer in mice. Since MitoQ already successfully passed Phase I clinical trials, our findings support the development of this drug as a preventive treatment against breast cancer metastasis. ABSTRACT: In oncology, the occurrence of distant metastases often marks the transition from curative to palliative care. Such outcome is highly predictable for breast cancer patients, even if tumors are detected early, and there is no specific treatment to prevent metastasis. Previous observations indicated that cancer cell mitochondria are bioenergetic sensors of the tumor microenvironment that produce superoxide to promote evasion. Here, we tested whether mitochondria-targeted antioxidant MitoQ is capable to prevent metastasis in the MDA-MB-231 model of triple-negative human breast cancer in mice and in the MMTV-PyMT model of spontaneously metastatic mouse breast cancer. At clinically relevant doses, we report that MitoQ not only prevented metastatic take and dissemination, but also local recurrence after surgery. We further provide in vitro evidence that MitoQ does not interfere with conventional chemotherapies used to treat breast cancer patients. Since MitoQ already successfully passed Phase I safety clinical trials, our preclinical data collectively provide a strong incentive to test this drug for the prevention of cancer dissemination and relapse in clinical trials with breast cancer patients. MDPI 2022-03-15 /pmc/articles/PMC8946761/ /pubmed/35326639 http://dx.doi.org/10.3390/cancers14061488 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Capeloa, Tania
Krzystyniak, Joanna
Rodriguez, Amanda Canas
Payen, Valéry L.
Zampieri, Luca X.
Pranzini, Erica
Derouane, Françoise
Vazeille, Thibaut
Bouzin, Caroline
Duhoux, François P.
Murphy, Michael P.
Porporato, Paolo E.
Sonveaux, Pierre
MitoQ Prevents Human Breast Cancer Recurrence and Lung Metastasis in Mice †
title MitoQ Prevents Human Breast Cancer Recurrence and Lung Metastasis in Mice †
title_full MitoQ Prevents Human Breast Cancer Recurrence and Lung Metastasis in Mice †
title_fullStr MitoQ Prevents Human Breast Cancer Recurrence and Lung Metastasis in Mice †
title_full_unstemmed MitoQ Prevents Human Breast Cancer Recurrence and Lung Metastasis in Mice †
title_short MitoQ Prevents Human Breast Cancer Recurrence and Lung Metastasis in Mice †
title_sort mitoq prevents human breast cancer recurrence and lung metastasis in mice †
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946761/
https://www.ncbi.nlm.nih.gov/pubmed/35326639
http://dx.doi.org/10.3390/cancers14061488
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