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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,...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
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.
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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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