Preclinical study of a Kv11.1 potassium channel activator as antineoplastic approach for breast cancer
| Autor: | Sarah Burris, Miranda Burnette, Jeremiah J. Zartman, Eun-Kyoung Breuer, Saverio Gentile, Vidhya R. Rao, Simon Kaja, Daniela Fukushiro-Lopes, Debra Wyatt, Andrew T. Baker, Clodia Osipo, Dimitrios E. Kouzoukas, W. Keith Jones, Alexandra D. Hegel |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Senescence senescence Activator (genetics) Chemistry DNA damage ion channels Potassium channel activator medicine.disease activator 03 medical and health sciences Therapeutic approach 030104 developmental biology 0302 clinical medicine Breast cancer Oncology In vivo 030220 oncology & carcinogenesis medicine Cancer research cancer therapy Ion channel Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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