SIRT1 is involved in adrenocortical cancer growth and motility.

Abstract

Adrenocortical cancer (ACC) is a rare tumour with unfavourable prognosis, lacking an effective treatment. This tumour is characterized by IGF-II (insulin-like growth factor II) overproduction, aromatase and ERα (oestrogen receptor alpha) up-regulation. Previous reports suggest that ERα expression can be regulated by sirt1 (sirtuin 1), a nicotinamide adenine dinucleotide (NAD+)-dependent 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/ERα 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.

• Authors: Adele Chimento, Arianna De Luca, Marta Claudia Nocito, Sara Sculco, Paola Avena, Davide La Padula, Lucia Zavaglia, Rosa Sirianni, Ivan Casaburi, Vincenzo Pezzi
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 25 Issue 8 Pg. 3856-3869 (04 2021) ISSN: 1582-4934 [Electronic] England
• PMID: 33650791 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• RNA, Small Interfering
• SIRT1 protein, human
• Sirtuin 1

Topics

• Adrenal Cortex Neoplasms (genetics, metabolism, pathology)
• Apoptosis
• Cell Movement
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Humans
• RNA, Small Interfering (genetics)
• Sirtuin 1 (antagonists & inhibitors, genetics, metabolism)
• Tumor Cells, Cultured