Molecular Mechanisms of Mitotane Action in Adrenocortical Cancer Based on In Vitro Studies

Mitotane is the only approved drug for the treatment of advanced adrenocortical carcinoma and is increasingly used for postoperative adjuvant therapy. Mitotane action involves the deregulation of cytochromes P450 enzymes, depolarization of mitochondrial membranes, and accumulation of free cholestero...

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Autores principales:	Marco Lo Iacono, Soraya Puglisi, Paola Perotti, Laura Saba, Jessica Petiti, Claudia Giachino, Giuseppe Reimondo, Massimo Terzolo
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mitotane adrenocortical carcinoma H295 strains Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/0fa15dcc1fd64291ae06db3812e4c83f
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spelling	oai:doaj.org-article:0fa15dcc1fd64291ae06db3812e4c83f2021-11-11T15:26:24ZMolecular Mechanisms of Mitotane Action in Adrenocortical Cancer Based on In Vitro Studies10.3390/cancers132152552072-6694https://doaj.org/article/0fa15dcc1fd64291ae06db3812e4c83f2021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5255https://doaj.org/toc/2072-6694Mitotane is the only approved drug for the treatment of advanced adrenocortical carcinoma and is increasingly used for postoperative adjuvant therapy. Mitotane action involves the deregulation of cytochromes P450 enzymes, depolarization of mitochondrial membranes, and accumulation of free cholesterol, leading to cell death. Although it is known that mitotane destroys the adrenal cortex and impairs steroidogenesis, its exact mechanism of action is still unclear. The most used cell models are H295-derived cell strains and SW13 cell lines. The diverging results obtained in presumably identical cell lines highlight the need for a stable in vitro model and/or a standard methodology to perform experiments on H295 strains. The presence of several enzymatic targets responsive to mitotane in mitochondria and mitochondria-associated membranes causes progressive alteration in mitochondrial structure when cells were exposed to mitotane. Confounding factors of culture affecting in vitro experiments could reduce the significance of any molecular mechanism identified in vitro. To ensure experimental reproducibility, particular care should be taken in the choice of culture conditions: aspects such as cell strains, culture serum, lipoproteins concentration, and culture passages should be carefully considered and explicated in the presentation of results. We aimed to review in vitro studies on mitotane effects, highlighting how different experimental conditions might contribute to the controversial findings. If the concerns pointed out in this review will be overcome, the new insights into mitotane mechanism of action observed in-vitro could allow the identification of novel pharmacological molecular pathways to be used to implement personalized therapy.Marco Lo IaconoSoraya PuglisiPaola PerottiLaura SabaJessica PetitiClaudia GiachinoGiuseppe ReimondoMassimo TerzoloMDPI AGarticlemitotaneadrenocortical carcinomaH295 strainsNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5255, p 5255 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mitotane adrenocortical carcinoma H295 strains Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	mitotane adrenocortical carcinoma H295 strains Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Marco Lo Iacono Soraya Puglisi Paola Perotti Laura Saba Jessica Petiti Claudia Giachino Giuseppe Reimondo Massimo Terzolo Molecular Mechanisms of Mitotane Action in Adrenocortical Cancer Based on In Vitro Studies
description	Mitotane is the only approved drug for the treatment of advanced adrenocortical carcinoma and is increasingly used for postoperative adjuvant therapy. Mitotane action involves the deregulation of cytochromes P450 enzymes, depolarization of mitochondrial membranes, and accumulation of free cholesterol, leading to cell death. Although it is known that mitotane destroys the adrenal cortex and impairs steroidogenesis, its exact mechanism of action is still unclear. The most used cell models are H295-derived cell strains and SW13 cell lines. The diverging results obtained in presumably identical cell lines highlight the need for a stable in vitro model and/or a standard methodology to perform experiments on H295 strains. The presence of several enzymatic targets responsive to mitotane in mitochondria and mitochondria-associated membranes causes progressive alteration in mitochondrial structure when cells were exposed to mitotane. Confounding factors of culture affecting in vitro experiments could reduce the significance of any molecular mechanism identified in vitro. To ensure experimental reproducibility, particular care should be taken in the choice of culture conditions: aspects such as cell strains, culture serum, lipoproteins concentration, and culture passages should be carefully considered and explicated in the presentation of results. We aimed to review in vitro studies on mitotane effects, highlighting how different experimental conditions might contribute to the controversial findings. If the concerns pointed out in this review will be overcome, the new insights into mitotane mechanism of action observed in-vitro could allow the identification of novel pharmacological molecular pathways to be used to implement personalized therapy.
format	article
author	Marco Lo Iacono Soraya Puglisi Paola Perotti Laura Saba Jessica Petiti Claudia Giachino Giuseppe Reimondo Massimo Terzolo
author_facet	Marco Lo Iacono Soraya Puglisi Paola Perotti Laura Saba Jessica Petiti Claudia Giachino Giuseppe Reimondo Massimo Terzolo
author_sort	Marco Lo Iacono
title	Molecular Mechanisms of Mitotane Action in Adrenocortical Cancer Based on In Vitro Studies
title_short	Molecular Mechanisms of Mitotane Action in Adrenocortical Cancer Based on In Vitro Studies
title_full	Molecular Mechanisms of Mitotane Action in Adrenocortical Cancer Based on In Vitro Studies
title_fullStr	Molecular Mechanisms of Mitotane Action in Adrenocortical Cancer Based on In Vitro Studies
title_full_unstemmed	Molecular Mechanisms of Mitotane Action in Adrenocortical Cancer Based on In Vitro Studies
title_sort	molecular mechanisms of mitotane action in adrenocortical cancer based on in vitro studies
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0fa15dcc1fd64291ae06db3812e4c83f
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Molecular Mechanisms of Mitotane Action in Adrenocortical Cancer Based on In Vitro Studies

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