{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:27:49Z","timestamp":1788265669397,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T00:00:00Z","timestamp":1649808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008672","name":"Wilhelm Sander Stiftung","doi-asserted-by":"publisher","award":["2019.115.1"],"award-info":[{"award-number":["2019.115.1"]}],"id":[{"id":"10.13039\/100008672","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Despite several new developments in the treatment of multiple myeloma, all available therapies are only palliative without curative potential and all patients ultimately relapse. Thus, novel therapeutic options are urgently required to prolong survival of or to even cure myeloma. Here, we show that multiple myeloma cells express the potassium channel Kv1.3 in their mitochondria. The mitochondrial Kv1.3 inhibitors PAPTP and PCARBTP are efficient against two tested human multiple myeloma cell lines (L-363 and RPMI-8226) and against ex vivo cultured, patient-derived myeloma cells, while healthy bone marrow cells are spared from toxicity. Cell death after treatment with PAPTP and PCARBTP occurs via the mitochondrial apoptotic pathway. In addition, we identify up-regulation of the multidrug resistance pump MDR-1 as the main potential resistance mechanism. Combination with ABT-199 (venetoclax), an inhibitor of Bcl2, has a synergistic effect, suggesting that mitochondrial Kv1.3 inhibitors could potentially be used as combination partner to venetoclax, even in the treatment of t(11;14) negative multiple myeloma, which represent the major part of cases and are rather resistant to venetoclax alone. We thus identify mitochondrial Kv1.3 channels as druggable targets against multiple myeloma.<\/jats:p>","DOI":"10.3390\/cancers14081955","type":"journal-article","created":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T21:33:42Z","timestamp":1649885622000},"page":"1955","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Mitochondrial Kv1.3 Channels as Target for Treatment of Multiple Myeloma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6430-1230","authenticated-orcid":false,"given":"Stephanie","family":"Kadow","sequence":"first","affiliation":[{"name":"Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8703-3275","authenticated-orcid":false,"given":"Fabian","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Freie University Berlin, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Kramer","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Hessler","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Scholtysik","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Oubari","sequence":"additional","affiliation":[{"name":"Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3265-8689","authenticated-orcid":false,"given":"Patricia","family":"Johansson","sequence":"additional","affiliation":[{"name":"Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"H\u00fcttmann","sequence":"additional","affiliation":[{"name":"Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Christian","family":"Reinhardt","sequence":"additional","affiliation":[{"name":"Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkhard","family":"Kleuser","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Freie University Berlin, 14195 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8284-2524","authenticated-orcid":false,"given":"Mario","family":"Zoratti","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padova, 35121 Padova, Italy"},{"name":"CNR Institute of Neuroscience, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2023-0749","authenticated-orcid":false,"given":"Andrea","family":"Mattarei","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ildiko","family":"Szab\u00f2","sequence":"additional","affiliation":[{"name":"CNR Institute of Neuroscience, 35121 Padova, Italy"},{"name":"Department of Biology, University of Padova, 35121 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich","family":"Gulbins","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Carpinteiro","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany"},{"name":"Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, 45147 Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Solimando, A.G., Da Via, M.C., Cicco, S., Leone, P., Di Lernia, G., Giannico, D., Desantis, V., Frassanito, M.A., Morizio, A., and Delgado Tascon, J. 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