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Biological response of adrenal carcinoma and melanoma cells to mitotane treatment

A previous case report described an adrenal incidentaloma initially misdiagnosed as adrenocortical carcinoma (ACC), which was treated with mitotane. The final diagnosis was metastatic melanoma of unknown primary origin. However, the patient developed rapid disease progression after mitotane withdraw...

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Autores principales: Stelcer, Ewelina, Komarowska, Hanna, Jopek, Karol, Żok, Agnieszka, Iżycki, Dariusz, Malińska, Agnieszka, Szczepaniak, Beata, Komekbai, Zhanat, Karczewski, Marek, Wierzbicki, Tomasz, Suchorska, Wiktoria Maria, Ruchała, Marek, Ruciński, Marcin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855164/
https://www.ncbi.nlm.nih.gov/pubmed/35261634
http://dx.doi.org/10.3892/ol.2022.13240
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author Stelcer, Ewelina
Komarowska, Hanna
Jopek, Karol
Żok, Agnieszka
Iżycki, Dariusz
Malińska, Agnieszka
Szczepaniak, Beata
Komekbai, Zhanat
Karczewski, Marek
Wierzbicki, Tomasz
Suchorska, Wiktoria Maria
Ruchała, Marek
Ruciński, Marcin
author_facet Stelcer, Ewelina
Komarowska, Hanna
Jopek, Karol
Żok, Agnieszka
Iżycki, Dariusz
Malińska, Agnieszka
Szczepaniak, Beata
Komekbai, Zhanat
Karczewski, Marek
Wierzbicki, Tomasz
Suchorska, Wiktoria Maria
Ruchała, Marek
Ruciński, Marcin
author_sort Stelcer, Ewelina
collection PubMed
description A previous case report described an adrenal incidentaloma initially misdiagnosed as adrenocortical carcinoma (ACC), which was treated with mitotane. The final diagnosis was metastatic melanoma of unknown primary origin. However, the patient developed rapid disease progression after mitotane withdrawal, suggesting a protective role for mitotane in a non-adrenal-derived tumor. The aim of the present study was to determine the biological response of primary melanoma cells obtained from that patient, and that of other established melanoma and ACC cell lines, to mitotane treatment using a proliferation assay, flow cytometry, quantitative PCR and microarrays. Although mitotane inhibited the proliferation of both ACC and melanoma cells, its role in melanoma treatment appears to be limited. Flow cytometry analysis and transcriptomic studies indicated that the ACC cell line was highly responsive to mitotane treatment, while the primary melanoma cells showed a moderate response in vitro. Mitotane modified the activity of several key biological processes, including ‘mitotic nuclear division’, ‘DNA repair’, ‘angiogenesis’ and ‘negative regulation of ERK1 and ERK2 cascade’. Mitotane administration led to elevated levels of DNA double-strand breaks, necrosis and apoptosis. The present study provides a comprehensive insight into the biological response of mitotane-treated cells at the molecular level. Notably, the present findings offer new knowledge on the effects of mitotane on ACC and melanoma cells.
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spelling pubmed-88551642022-03-07 Biological response of adrenal carcinoma and melanoma cells to mitotane treatment Stelcer, Ewelina Komarowska, Hanna Jopek, Karol Żok, Agnieszka Iżycki, Dariusz Malińska, Agnieszka Szczepaniak, Beata Komekbai, Zhanat Karczewski, Marek Wierzbicki, Tomasz Suchorska, Wiktoria Maria Ruchała, Marek Ruciński, Marcin Oncol Lett Articles A previous case report described an adrenal incidentaloma initially misdiagnosed as adrenocortical carcinoma (ACC), which was treated with mitotane. The final diagnosis was metastatic melanoma of unknown primary origin. However, the patient developed rapid disease progression after mitotane withdrawal, suggesting a protective role for mitotane in a non-adrenal-derived tumor. The aim of the present study was to determine the biological response of primary melanoma cells obtained from that patient, and that of other established melanoma and ACC cell lines, to mitotane treatment using a proliferation assay, flow cytometry, quantitative PCR and microarrays. Although mitotane inhibited the proliferation of both ACC and melanoma cells, its role in melanoma treatment appears to be limited. Flow cytometry analysis and transcriptomic studies indicated that the ACC cell line was highly responsive to mitotane treatment, while the primary melanoma cells showed a moderate response in vitro. Mitotane modified the activity of several key biological processes, including ‘mitotic nuclear division’, ‘DNA repair’, ‘angiogenesis’ and ‘negative regulation of ERK1 and ERK2 cascade’. Mitotane administration led to elevated levels of DNA double-strand breaks, necrosis and apoptosis. The present study provides a comprehensive insight into the biological response of mitotane-treated cells at the molecular level. Notably, the present findings offer new knowledge on the effects of mitotane on ACC and melanoma cells. D.A. Spandidos 2022-04 2022-02-10 /pmc/articles/PMC8855164/ /pubmed/35261634 http://dx.doi.org/10.3892/ol.2022.13240 Text en Copyright: © Stelcer et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Stelcer, Ewelina
Komarowska, Hanna
Jopek, Karol
Żok, Agnieszka
Iżycki, Dariusz
Malińska, Agnieszka
Szczepaniak, Beata
Komekbai, Zhanat
Karczewski, Marek
Wierzbicki, Tomasz
Suchorska, Wiktoria Maria
Ruchała, Marek
Ruciński, Marcin
Biological response of adrenal carcinoma and melanoma cells to mitotane treatment
title Biological response of adrenal carcinoma and melanoma cells to mitotane treatment
title_full Biological response of adrenal carcinoma and melanoma cells to mitotane treatment
title_fullStr Biological response of adrenal carcinoma and melanoma cells to mitotane treatment
title_full_unstemmed Biological response of adrenal carcinoma and melanoma cells to mitotane treatment
title_short Biological response of adrenal carcinoma and melanoma cells to mitotane treatment
title_sort biological response of adrenal carcinoma and melanoma cells to mitotane treatment
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855164/
https://www.ncbi.nlm.nih.gov/pubmed/35261634
http://dx.doi.org/10.3892/ol.2022.13240
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