{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T05:51:55Z","timestamp":1780552315383,"version":"3.54.1"},"reference-count":46,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T00:00:00Z","timestamp":1638748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007076","name":"Italian Association for Cancer Research","doi-asserted-by":"publisher","award":["IG 21558"],"award-info":[{"award-number":["IG 21558"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministry of Education, Universities and Research","doi-asserted-by":"publisher","award":["PRIN 20174TB8KW"],"award-info":[{"award-number":["PRIN 20174TB8KW"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cancers13236144","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T02:48:13Z","timestamp":1638845293000},"page":"6144","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["NS-11021 Modulates Cancer-Associated Processes Independently of BK Channels in Melanoma and Pancreatic Duct Adenocarcinoma Cell Lines"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9934-293X","authenticated-orcid":false,"given":"Alessia","family":"Remigante","sequence":"first","affiliation":[{"name":"Biophysics Institute, National Research Council, 16149 Genoa, Italy"},{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Zuccolini","sequence":"additional","affiliation":[{"name":"Biophysics Institute, National Research Council, 16149 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Barbieri","sequence":"additional","affiliation":[{"name":"Biophysics Institute, National Research Council, 16149 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0528-1158","authenticated-orcid":false,"given":"Loretta","family":"Ferrera","sequence":"additional","affiliation":[{"name":"U.O.C. Genetica Medica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4904-4963","authenticated-orcid":false,"given":"Rossana","family":"Morabito","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Gavazzo","sequence":"additional","affiliation":[{"name":"Biophysics Institute, National Research Council, 16149 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8644-8847","authenticated-orcid":false,"given":"Michael","family":"Pusch","sequence":"additional","affiliation":[{"name":"Biophysics Institute, National Research Council, 16149 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6512-1802","authenticated-orcid":false,"given":"Cristiana","family":"Picco","sequence":"additional","affiliation":[{"name":"Biophysics Institute, National Research Council, 16149 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.intimp.2014.06.040","article-title":"Big Potassium (BK) ion channels in biology, disease and possible targets for cancer immunotherapy","volume":"22","author":"Ge","year":"2014","journal-title":"Int. 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