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Preclinical study of a Kv11.1 potassium channel activator as antineoplastic approach for breast cancer
Potassium ion (K(+)) channels have been recently found to play a critical role in cancer biology. Despite that pharmacologic manipulation of ion channels is recognized as an important therapeutic approach, very little is known about the effects of targeting of K(+) channels in cancer. In this study,...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790466/ https://www.ncbi.nlm.nih.gov/pubmed/29423049 http://dx.doi.org/10.18632/oncotarget.22925 |
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author | Fukushiro-Lopes, Daniela F. Hegel, Alexandra D. Rao, Vidhya Wyatt, Debra Baker, Andrew Breuer, Eun-Kyoung Osipo, Clodia Zartman, Jeremiah J. Burnette, Miranda Kaja, Simon Kouzoukas, Dimitrios Burris, Sarah Jones, W. Keith Gentile, Saverio |
author_facet | Fukushiro-Lopes, Daniela F. Hegel, Alexandra D. Rao, Vidhya Wyatt, Debra Baker, Andrew Breuer, Eun-Kyoung Osipo, Clodia Zartman, Jeremiah J. Burnette, Miranda Kaja, Simon Kouzoukas, Dimitrios Burris, Sarah Jones, W. Keith Gentile, Saverio |
author_sort | Fukushiro-Lopes, Daniela F. |
collection | PubMed |
description | Potassium ion (K(+)) channels have been recently found to play a critical role in cancer biology. Despite that pharmacologic manipulation of ion channels is recognized as an important therapeutic approach, very little is known about the effects of targeting of K(+) channels in cancer. In this study, we demonstrate that use of the Kv11.1 K(+) channel activator NS1643 inhibits tumor growth in an in vivo model of breast cancer. Tumors exposed to NS1643 had reduced levels of proliferation markers, high expression levels of senescence markers, increased production of ROS and DNA damage compared to tumors of untreated mice. Importantly, mice treated with NS1643 did not exhibit significant cardiac dysfunction. In conclusion, pharmacological stimulation of Kv11.1 activity produced arrested TNBC-derived tumor growth by generating DNA damage and senescence without significant side effects. We propose that use of Kv11.1 channels activators could be considered as a possible pharmacological strategy against breast tumors. |
format | Online Article Text |
id | pubmed-5790466 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-57904662018-02-08 Preclinical study of a Kv11.1 potassium channel activator as antineoplastic approach for breast cancer Fukushiro-Lopes, Daniela F. Hegel, Alexandra D. Rao, Vidhya Wyatt, Debra Baker, Andrew Breuer, Eun-Kyoung Osipo, Clodia Zartman, Jeremiah J. Burnette, Miranda Kaja, Simon Kouzoukas, Dimitrios Burris, Sarah Jones, W. Keith Gentile, Saverio Oncotarget Research Paper Potassium ion (K(+)) channels have been recently found to play a critical role in cancer biology. Despite that pharmacologic manipulation of ion channels is recognized as an important therapeutic approach, very little is known about the effects of targeting of K(+) channels in cancer. In this study, we demonstrate that use of the Kv11.1 K(+) channel activator NS1643 inhibits tumor growth in an in vivo model of breast cancer. Tumors exposed to NS1643 had reduced levels of proliferation markers, high expression levels of senescence markers, increased production of ROS and DNA damage compared to tumors of untreated mice. Importantly, mice treated with NS1643 did not exhibit significant cardiac dysfunction. In conclusion, pharmacological stimulation of Kv11.1 activity produced arrested TNBC-derived tumor growth by generating DNA damage and senescence without significant side effects. We propose that use of Kv11.1 channels activators could be considered as a possible pharmacological strategy against breast tumors. Impact Journals LLC 2017-12-04 /pmc/articles/PMC5790466/ /pubmed/29423049 http://dx.doi.org/10.18632/oncotarget.22925 Text en Copyright: © 2018 Fukushiro-Lopes et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Fukushiro-Lopes, Daniela F. Hegel, Alexandra D. Rao, Vidhya Wyatt, Debra Baker, Andrew Breuer, Eun-Kyoung Osipo, Clodia Zartman, Jeremiah J. Burnette, Miranda Kaja, Simon Kouzoukas, Dimitrios Burris, Sarah Jones, W. Keith Gentile, Saverio Preclinical study of a Kv11.1 potassium channel activator as antineoplastic approach for breast cancer |
title | Preclinical study of a Kv11.1 potassium channel activator as antineoplastic approach for breast cancer |
title_full | Preclinical study of a Kv11.1 potassium channel activator as antineoplastic approach for breast cancer |
title_fullStr | Preclinical study of a Kv11.1 potassium channel activator as antineoplastic approach for breast cancer |
title_full_unstemmed | Preclinical study of a Kv11.1 potassium channel activator as antineoplastic approach for breast cancer |
title_short | Preclinical study of a Kv11.1 potassium channel activator as antineoplastic approach for breast cancer |
title_sort | preclinical study of a kv11.1 potassium channel activator as antineoplastic approach for breast cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790466/ https://www.ncbi.nlm.nih.gov/pubmed/29423049 http://dx.doi.org/10.18632/oncotarget.22925 |
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