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This criterion is clearly fulfilled by desethylamiodarone (DEA), which is a major metabolite of amiodarone, a widely used antiarrhythmic drug, since the DEA previously demonstrated anti-neoplastic, anti-metastasizing, and direct mitochondrial effects in B16F10 melanoma cells. Additionally, the more than fifty years of clinical experience with amiodarone should answer most of the safety concerns about DEA. Accordingly, in the present study, we investigated DEA\u2019s potential in TNBC by using a TN and a hormone receptor positive (HR+) BC cell line. DEA reduced the viability, colony formation, and invasive growth of the 4T1 cell line and led to a higher extent of the MCF-7 cell line. It lowered mitochondrial transmembrane potential and induced mitochondrial fragmentation. On the other hand, DEA failed to significantly affect various parameters of the cellular energy metabolism as determined by a Seahorse live cell respirometer. Cyclooxygenase 2 (COX-2), which was upregulated by DEA in the TNBC cell line only, accounted for most of 4T1\u2019s DEA resistance, which was counteracted by the selective COX-2 inhibitor celecoxib. All these data indicate that DEA may have potentiality in the therapy of TNBC.<\/jats:p>","DOI":"10.3390\/ijms23031544","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T05:26:17Z","timestamp":1643433977000},"page":"1544","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Involvement of Mitochondrial Mechanisms and Cyclooxygenase-2 Activation in the Effect of Desethylamiodarone on 4T1 Triple-Negative Breast Cancer Line"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1906-4333","authenticated-orcid":false,"suffix":"Jr.","given":"Ferenc","family":"Gallyas","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of Pecs Medical School, 7624 Pecs, Hungary"},{"name":"Szentagothai Research Centre, University of Pecs, 7624 Pecs, Hungary"},{"name":"LERN-UP Nuclear-Mitochondrial Interactions Research Group, 1245 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3910-1725","authenticated-orcid":false,"given":"Fadi H. J.","family":"Ramadan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kitti","family":"Andreidesz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eniko","family":"Hocsak","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliz","family":"Szabo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antal","family":"Tapodi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyongyi N.","family":"Kiss","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin","family":"Fekete","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Bognar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpad","family":"Szanto","sequence":"additional","affiliation":[{"name":"Urology Clinic, UP Medical Center, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0582-7755","authenticated-orcid":false,"given":"Zita","family":"Bognar","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of Pecs Medical School, 7624 Pecs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/35021093","article-title":"Molecular portraits of human breast tumours","volume":"406","author":"Perou","year":"2000","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"120","DOI":"10.5306\/wjco.v8.i2.120","article-title":"Targeted therapies in breast cancer: New challenges to fight against resistance","volume":"8","author":"Masoud","year":"2017","journal-title":"World J. 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