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Previous reports suggest that ER\u03b1 expression can be regulated by sirt1 (sirtuin 1), a nicotinamide adenine dinucleotide (NAD+)\u2010dependent class III histone deacetylases that modulates activity of several substrates involved in cellular stress, metabolism, proliferation, senescence, protein degradation and apoptosis. Nevertheless, sirt1 can act as a tumour suppressor or oncogenic protein. In this study, we found that in H295R and SW13 cell lines, sirt1 expression is inhibited by sirtinol, a potent inhibitor of sirt1 activity. In addition, sirtinol is able to decrease ACC cell proliferation, colony and spheroids formation and to activate the intrinsic apoptotic mechanism. Particularly, we observed that sirtinol interferes with E2\/ER\u03b1 and IGF1R (insulin growth factor 1 receptor) pathways by decreasing receptors expression. Sirt1 involvement was confirmed by using a specific sirt1 siRNA. More importantly, we observed that sirtinol can synergize with mitotane, a selective adrenolitic drug, in inhibiting adrenocortical cancer cell growth. Collectively, our data reveal an oncogenic role for sirt1 in ACC and its targeting could implement treatment options for this type of cancer.<\/jats:p>","DOI":"10.1111\/jcmm.16317","type":"journal-article","created":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T13:54:05Z","timestamp":1614693245000},"page":"3856-3869","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["SIRT1 is involved in adrenocortical cancer growth and motility"],"prefix":"10.1111","volume":"25","author":[{"given":"Adele","family":"Chimento","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Health and Nutritional Sciences University of Calabria Arcavacata di Rende, Cosenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Health and Nutritional Sciences University of Calabria Arcavacata di Rende, 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