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Article

NS-11021 Modulates Cancer-Associated Processes Independently of BK Channels in Melanoma and Pancreatic Duct Adenocarcinoma Cell Lines

1
Biophysics Institute, National Research Council, 16149 Genoa, Italy
2
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
3
U.O.C. Genetica Medica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Giannina Gaslini, 16147 Genoa, Italy
*
Author to whom correspondence should be addressed.
These authors shared senior authorship.
Academic Editor: Luis A. Pardo
Cancers 2021, 13(23), 6144; https://doi.org/10.3390/cancers13236144
Received: 27 October 2021 / Revised: 2 December 2021 / Accepted: 4 December 2021 / Published: 6 December 2021
(This article belongs to the Collection Ion Channels in Cancer Therapies)
Potassium channels permit the selective passage of K+ ions across the cell me brane and are important for setting the membrane potential and for the transmission of electrical signals in all cells. Ca2+ activated K+ channels provide a means to couple intracellular calcium signaling to changes of the membrane potential. Among these, the large-conductance Ca2+-activated K+ channel, known as BK, has been proposed to be involved in several cancer-associated processes. In the present work, we tested various BK channel activators for anti-cancer effects in melanoma and pancreatic duct carcinoma cell lines. Only one of the activators (NS-11021) had effects on cancer-associated processes. However, the compound, as a side-effect, also increased the intracellular Ca2+ concentration independently of BK channel activation. Overall, we conclude that the activation of the BK channel by itself is not sufficient to produce beneficial anti-cancer effects.
Potassium channels have emerged as regulators of carcinogenesis, thus introducing possible new therapeutic strategies in the fight against cancer. In particular, the large-conductance Ca2+-activated K+ channel, often referred to as BK channel, is involved in several cancer-associated processes. Here, we investigated the effects of different BK activators, NS-11021, NS-19504, and BMS-191011, in IGR39 (primary melanoma cell line) and Panc-1 (primary pancreatic duct carcinoma cell line), highly expressing the channel, and in IGR37 (metastatic melanoma cell line) that barely express BK. Our data showed that NS-11021 and NS-19504 potently activated BK channels in IGR39 and Panc-1 cells, while no effect on channel activation was detected in IGR37 cells. On the contrary, BK channel activator BMS-191011 was less effective. However, only NS-11021 showed significant effects in cancer-associated processes, such as cell survival, migration, and proliferation in these cancer cell lines. Moreover, NS-11021 led to an increase of intracellular Ca2+ concentration, independent of BK channel activation, thus complicating any interpretation of its role in the regulation of cancer-associated mechanisms. Overall, we conclude that the activation of the BK channel by itself is not sufficient to produce beneficial anti-cancer effects in the melanoma and PDAC cell lines examined. Importantly, our results raise an alarm flag regarding the use of presumably specific BK channel openers as anti-cancer agents. View Full-Text
Keywords: BK channel; BK openers; calcium; IGR39 cells; Panc-1 cells; cancers BK channel; BK openers; calcium; IGR39 cells; Panc-1 cells; cancers
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MDPI and ACS Style

Remigante, A.; Zuccolini, P.; Barbieri, R.; Ferrera, L.; Morabito, R.; Gavazzo, P.; Pusch, M.; Picco, C. NS-11021 Modulates Cancer-Associated Processes Independently of BK Channels in Melanoma and Pancreatic Duct Adenocarcinoma Cell Lines. Cancers 2021, 13, 6144. https://doi.org/10.3390/cancers13236144

AMA Style

Remigante A, Zuccolini P, Barbieri R, Ferrera L, Morabito R, Gavazzo P, Pusch M, Picco C. NS-11021 Modulates Cancer-Associated Processes Independently of BK Channels in Melanoma and Pancreatic Duct Adenocarcinoma Cell Lines. Cancers. 2021; 13(23):6144. https://doi.org/10.3390/cancers13236144

Chicago/Turabian Style

Remigante, Alessia, Paolo Zuccolini, Raffaella Barbieri, Loretta Ferrera, Rossana Morabito, Paola Gavazzo, Michael Pusch, and Cristiana Picco. 2021. "NS-11021 Modulates Cancer-Associated Processes Independently of BK Channels in Melanoma and Pancreatic Duct Adenocarcinoma Cell Lines" Cancers 13, no. 23: 6144. https://doi.org/10.3390/cancers13236144

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