Research Papers:

Preclinical study of a Kv11.1 potassium channel activator as antineoplastic approach for breast cancer

Daniela F. Fukushiro-Lopes, Alexandra D. Hegel, Vidhya Rao, Debra Wyatt, Andrew Baker, Eun-Kyoung Breuer, Clodia Osipo, Jeremiah J. Zartman, Miranda Burnette, Simon Kaja, Dimitrios Kouzoukas, Sarah Burris, W. Keith Jones and Saverio Gentile _

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Oncotarget. 2018; 9:3321-3337. https://doi.org/10.18632/oncotarget.22925

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Daniela F. Fukushiro-Lopes1, Alexandra D. Hegel1, Vidhya Rao1,6, Debra Wyatt2, Andrew Baker2, Eun-Kyoung Breuer2, Clodia Osipo2, Jeremiah J. Zartman3, Miranda Burnette3, Simon Kaja1,5,6, Dimitrios Kouzoukas1, Sarah Burris4, W. Keith Jones1 and Saverio Gentile1

1Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA

2Department of Pathology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA

3Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN, USA

4Cardiovascular Research Institute, Loyola University Chicago, Maywood, IL, USA

5Department of Ophthalmology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA

6Research Service, Edward Hines Jr. VA Hospital, Hines, IL, USA

Correspondence to:

Saverio Gentile, email: [email protected]

Keywords: cancer therapy; ion channels; activator; DNA damage; senescence

Received: October 20, 2017     Accepted: November 09, 2017     Published: December 04, 2017


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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