{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:01:39Z","timestamp":1788930099869,"version":"build-2803163510"},"reference-count":49,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T00:00:00Z","timestamp":1638835200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Novartis Pharma A.G"},{"DOI":"10.13039\/501100007343","name":"University of Brescia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007343","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017659","name":"Uniscientia Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Mitotane is the only approved drug for treating adrenocortical carcinoma (ACC). The regimen added to mitotane is chemotherapy with etoposide, doxorubicin, and cisplatin. This pharmacological approach, however, has a limited efficacy and significant toxicity. Target-therapy agents represent a new promising approach to cancer therapy. Among these, a preeminent role is played by agents that interfere with cell-cycle progression, such as CDK4\/6-inhibitors. Here, we investigate whether ribociclib could induce a cytotoxic effect both in ACC cell line and patient-derived primary cell cultures, alone or in combined settings. Cell viability was determined by 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide assay, whereas cell proliferation was evaluated by direct count. Binary combination experiments were performed using Chou and Talalay method. Gene expression was analyzed by quantitative RT-PCR, whereas protein expression was evaluated by immunofluorescence. A double staining assay revealed that ribociclib induced a prevalent apoptotic cell death. Cell-cycle analysis was performed to evaluate the effect of ribociclib treatment on cell-cycle progression in ACC cell models. Our results indicate that ribociclib was cytotoxic and reduced the cell proliferation rate. The effect on cell viability was enhanced when ribociclib was combined with progesterone and\/or mitotane. The effect of ribociclib on cell-cycle progression revealed a drug-induced cell accumulation in G2 phase. The positive relationship underlined by our results between ribociclib, progesterone, and mitotane strengthen the clinical potential of this combination.<\/jats:p>","DOI":"10.1210\/endocr\/bqab248","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T21:31:15Z","timestamp":1638912675000},"source":"Crossref","is-referenced-by-count":13,"title":["Ribociclib Cytotoxicity Alone or Combined With Progesterone and\/or Mitotane in in Vitro Adrenocortical Carcinoma Cells"],"prefix":"10.1210","volume":"163","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0835-0916","authenticated-orcid":false,"given":"Andrea","family":"Abate","sequence":"first","affiliation":[{"name":"Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, 25123, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Rossini","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, 25123, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariangela","family":"Tamburello","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, 25123, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Lagan\u00e0","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, 25123, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Cosentini","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, 25123, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6922-1934","authenticated-orcid":false,"given":"Salvatore","family":"Grisanti","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, 25123, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Fiorentini","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, 25123, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido A M","family":"Tiberio","sequence":"additional","affiliation":[{"name":"Surgical Clinic, Department of Clinical and Experimental Sciences, University of Brescia at ASST Spedali Civili di Brescia, Brescia, 25123, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Scatolini","sequence":"additional","affiliation":[{"name":"Molecular Oncology Laboratory, \u201cEdo ed Elvo Tempia\u201d Foundation, Ponderano, 13875, Biella, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Grosso","sequence":"additional","affiliation":[{"name":"Molecular Oncology Laboratory, \u201cEdo ed Elvo Tempia\u201d Foundation, Ponderano, 13875, Biella, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constanze","family":"Hantel","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland"},{"name":"Medizinische Klinik und Poliklinik III, University Hospital Carl Gustav Carus Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7543-0289","authenticated-orcid":false,"given":"Maurizio","family":"Memo","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, 25123, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3956-0043","authenticated-orcid":false,"given":"Alfredo","family":"Berruti","sequence":"additional","affiliation":[{"name":"Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, 25123, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Sigala","sequence":"additional","affiliation":[{"name":"Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, 25123, 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Oncol."},{"issue":"3","key":"2022011219440756800_CIT0003","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1677\/erc.1.01025","article-title":"Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial","volume":"12","author":"Berruti","year":"2005","journal-title":"Endocr Relat Cancer."},{"issue":"4","key":"2022011219440756800_CIT0004","doi-asserted-by":"crossref","first-page":"941","DOI":"10.3390\/cancers12040941","article-title":"Efficacy of the EDP-M scheme plus adjunctive surgery in the management of patients with advanced adrenocortical carcinoma: the Brescia experience","volume":"12","author":"Lagan\u00e0","year":"2020","journal-title":"Cancers (Basel)."},{"issue":"23","key":"2022011219440756800_CIT0005","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1056\/NEJMoa1200966","article-title":"Combination chemotherapy in advanced adrenocortical 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