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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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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 |
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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 |
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