Cargando…

SIRT1 is involved in adrenocortical cancer growth and motility

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 ca...

Descripción completa

Detalles Bibliográficos
Autores principales: Chimento, Adele, De Luca, Arianna, Nocito, Marta Claudia, Sculco, Sara, Avena, Paola, La Padula, Davide, Zavaglia, Lucia, Sirianni, Rosa, Casaburi, Ivan, Pezzi, Vincenzo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051751/
https://www.ncbi.nlm.nih.gov/pubmed/33650791
http://dx.doi.org/10.1111/jcmm.16317
_version_ 1783679791720824832
author Chimento, Adele
De Luca, Arianna
Nocito, Marta Claudia
Sculco, Sara
Avena, Paola
La Padula, Davide
Zavaglia, Lucia
Sirianni, Rosa
Casaburi, Ivan
Pezzi, Vincenzo
author_facet Chimento, Adele
De Luca, Arianna
Nocito, Marta Claudia
Sculco, Sara
Avena, Paola
La Padula, Davide
Zavaglia, Lucia
Sirianni, Rosa
Casaburi, Ivan
Pezzi, Vincenzo
author_sort Chimento, Adele
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8051751
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-80517512021-04-21 SIRT1 is involved in adrenocortical cancer growth and motility Chimento, Adele De Luca, Arianna Nocito, Marta Claudia Sculco, Sara Avena, Paola La Padula, Davide Zavaglia, Lucia Sirianni, Rosa Casaburi, Ivan Pezzi, Vincenzo J Cell Mol Med Original Articles 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. John Wiley and Sons Inc. 2021-03-02 2021-04 /pmc/articles/PMC8051751/ /pubmed/33650791 http://dx.doi.org/10.1111/jcmm.16317 Text en © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Chimento, Adele
De Luca, Arianna
Nocito, Marta Claudia
Sculco, Sara
Avena, Paola
La Padula, Davide
Zavaglia, Lucia
Sirianni, Rosa
Casaburi, Ivan
Pezzi, Vincenzo
SIRT1 is involved in adrenocortical cancer growth and motility
title SIRT1 is involved in adrenocortical cancer growth and motility
title_full SIRT1 is involved in adrenocortical cancer growth and motility
title_fullStr SIRT1 is involved in adrenocortical cancer growth and motility
title_full_unstemmed SIRT1 is involved in adrenocortical cancer growth and motility
title_short SIRT1 is involved in adrenocortical cancer growth and motility
title_sort sirt1 is involved in adrenocortical cancer growth and motility
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051751/
https://www.ncbi.nlm.nih.gov/pubmed/33650791
http://dx.doi.org/10.1111/jcmm.16317
work_keys_str_mv AT chimentoadele sirt1isinvolvedinadrenocorticalcancergrowthandmotility
AT delucaarianna sirt1isinvolvedinadrenocorticalcancergrowthandmotility
AT nocitomartaclaudia sirt1isinvolvedinadrenocorticalcancergrowthandmotility
AT sculcosara sirt1isinvolvedinadrenocorticalcancergrowthandmotility
AT avenapaola sirt1isinvolvedinadrenocorticalcancergrowthandmotility
AT lapaduladavide sirt1isinvolvedinadrenocorticalcancergrowthandmotility
AT zavaglialucia sirt1isinvolvedinadrenocorticalcancergrowthandmotility
AT siriannirosa sirt1isinvolvedinadrenocorticalcancergrowthandmotility
AT casaburiivan sirt1isinvolvedinadrenocorticalcancergrowthandmotility
AT pezzivincenzo sirt1isinvolvedinadrenocorticalcancergrowthandmotility