{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:46Z","timestamp":1787028526165,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T00:00:00Z","timestamp":1700784000000},"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":["IG2019-23069"],"award-info":[{"award-number":["IG2019-23069"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Mitotane is the only drug approved for the treatment of adrenocortical carcinoma (ACC). Although it has been used for many years, its mechanism of action remains elusive. H295R cells are, in ACC, an essential tool to evaluate drug mechanisms, although they often lead to conflicting results. Methods: Using different in vitro biomolecular technologies and biochemical\/biophysical experiments, we evaluated how the presence of \u201cconfounding factors\u201d in culture media and patient sera could reduce the pharmacological effect of mitotane and its metabolites. Results: We discovered that albumin, the most abundant protein in the blood, was able to bind mitotane. This interaction altered the effect of the drug by blocking its biological activity. This blocking effect was independent of the albumin source or methodology used and altered the assessment of drug sensitivity of the cell lines. Conclusions: In conclusion, we have for the first time demonstrated that albumin does not only act as an inert drug carrier when mitotane or its metabolites are present. Indeed, our experiments clearly indicated that both albumin and human serum were able to suppress the pharmacological effect of mitotane in vitro. These experiments could represent a first step towards the individualization of mitotane treatment in this rare tumor.<\/jats:p>","DOI":"10.3390\/ijms242316701","type":"journal-article","created":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T03:43:59Z","timestamp":1700797439000},"page":"16701","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Albumin\/Mitotane Interaction Affects Drug Activity in Adrenocortical Carcinoma Cells: Smoke and Mirrors on Mitotane Effect with Possible Implications for Patients\u2019 Management"],"prefix":"10.3390","volume":"24","author":[{"given":"Aurora","family":"Schiavon","sequence":"first","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9246-0511","authenticated-orcid":false,"given":"Laura","family":"Saba","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4593-4507","authenticated-orcid":false,"given":"Gianluca","family":"Catucci","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Systems Biology, University of Turin, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8640-2462","authenticated-orcid":false,"given":"Jessica","family":"Petiti","sequence":"additional","affiliation":[{"name":"Division of Advanced Materials Metrology and Life Sciences, Istituto Nazionale di Ricerca Metrologica (INRiM), 10135 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2883-6139","authenticated-orcid":false,"given":"Soraya","family":"Puglisi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Borin","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9489-2094","authenticated-orcid":false,"given":"Giuseppe","family":"Reimondo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6559-276X","authenticated-orcid":false,"given":"Gianfranco","family":"Gilardi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Systems Biology, University of Turin, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7957-3925","authenticated-orcid":false,"given":"Claudia","family":"Giachino","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4171-2851","authenticated-orcid":false,"given":"Massimo","family":"Terzolo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3936-4472","authenticated-orcid":false,"given":"Marco","family":"Lo Iacono","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bergenstal, D.M., Lipsett, M.B., Moy, R.H., and Hertz, R. 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