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Based on these data, we wanted to characterize the effects of IK blockers on melanoma metastatic cells and to understand if such effects were exclusively IK-dependent. For this purpose, we employed two different blockers, namely clotrimazole and senicapoc, and two cell lines: metastatic melanoma WM266-4 and pancreatic cancer Panc-1, which is reported to have little or no IK expression. Clotrimazole and senicapoc induced a decrease in viability and the migration of both WM266-4 and Panc-1 cells irrespective of IK expression levels. Patch-clamp experiments on WM266-4 cells revealed Ca2+-dependent, IK-like, clotrimazole- and senicapoc-sensitive currents, which could not be detected in Panc-1 cells. Neither clotrimazole nor senicapoc altered the intracellular Ca2+ concentration. These results suggest that the effects of IK blockers on cancer cells are not strictly dependent on a robust presence of the channel in the plasma membrane, but they might be due to off-target effects on other cellular targets or to the blockade of IK channels localized in intracellular organelles.<\/jats:p>","DOI":"10.3390\/ijms242216285","type":"journal-article","created":{"date-parts":[[2023,11,14]],"date-time":"2023-11-14T02:20:37Z","timestamp":1699928437000},"page":"16285","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["IK Channel-Independent Effects of Clotrimazole and Senicapoc on Cancer Cells Viability and Migration"],"prefix":"10.3390","volume":"24","author":[{"given":"Paolo","family":"Zuccolini","sequence":"first","affiliation":[{"name":"Biophysics Institute, National Research Council, 16149 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Barbieri","sequence":"additional","affiliation":[{"name":"Biophysics Institute, National Research Council, 16149 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Sbrana","sequence":"additional","affiliation":[{"name":"Biophysics Institute, National Research Council, 16149 Genova, 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 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2016-4702","authenticated-orcid":false,"given":"Paola","family":"Gavazzo","sequence":"additional","affiliation":[{"name":"Biophysics Institute, National Research Council, 16149 Genova, 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 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5732","DOI":"10.3748\/wjg.v25.i38.5732","article-title":"Role of ion channels in gastrointestinal cancer","volume":"25","author":"Anderson","year":"2019","journal-title":"World J. 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