CYP11B1 has no role in mitotane action and metabolism in adrenocortical carcinoma cells

Mitotane is the reference drug for adrenocortical carcinoma (ACC) and the metabolic activation of the drug is considered as essential for its activity. The aim of this study was to assess the role of CYP11B1 on mitotane action and metabolism in H295R ACC cells to understand whether this enzyme may i...

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Autores principales: Germano, Antonina, Saba, Laura, De Francia, Silvia, Rapa, Ida, Perotti, Paola, Berruti, Alfredo, Volante, Marco, Terzolo, Massimo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937768/
https://www.ncbi.nlm.nih.gov/pubmed/29734384
http://dx.doi.org/10.1371/journal.pone.0196931
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author Germano, Antonina
Saba, Laura
De Francia, Silvia
Rapa, Ida
Perotti, Paola
Berruti, Alfredo
Volante, Marco
Terzolo, Massimo
author_facet Germano, Antonina
Saba, Laura
De Francia, Silvia
Rapa, Ida
Perotti, Paola
Berruti, Alfredo
Volante, Marco
Terzolo, Massimo
author_sort Germano, Antonina
collection PubMed
description Mitotane is the reference drug for adrenocortical carcinoma (ACC) and the metabolic activation of the drug is considered as essential for its activity. The aim of this study was to assess the role of CYP11B1 on mitotane action and metabolism in H295R ACC cells to understand whether this enzyme may influence mitotane action. The simultaneous incubation with mitotane and metyrapone, an adrenolytic molecule targeting 11-beta-hydroxylase, did not influence mitotane-mediated cytotoxic effect and metabolism in H295R ACC cells. CYP11B1 silencing confirmed the lack of a significant metyrapone effect on mitotane action. The present findings do not support the view that CYP11B1 catalyzes a crucial step in the metabolic activation of mitotane and that CYP11B1 confers the adrenal specificity to mitotane.
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spelling pubmed-59377682018-05-18 CYP11B1 has no role in mitotane action and metabolism in adrenocortical carcinoma cells Germano, Antonina Saba, Laura De Francia, Silvia Rapa, Ida Perotti, Paola Berruti, Alfredo Volante, Marco Terzolo, Massimo PLoS One Research Article Mitotane is the reference drug for adrenocortical carcinoma (ACC) and the metabolic activation of the drug is considered as essential for its activity. The aim of this study was to assess the role of CYP11B1 on mitotane action and metabolism in H295R ACC cells to understand whether this enzyme may influence mitotane action. The simultaneous incubation with mitotane and metyrapone, an adrenolytic molecule targeting 11-beta-hydroxylase, did not influence mitotane-mediated cytotoxic effect and metabolism in H295R ACC cells. CYP11B1 silencing confirmed the lack of a significant metyrapone effect on mitotane action. The present findings do not support the view that CYP11B1 catalyzes a crucial step in the metabolic activation of mitotane and that CYP11B1 confers the adrenal specificity to mitotane. Public Library of Science 2018-05-07 /pmc/articles/PMC5937768/ /pubmed/29734384 http://dx.doi.org/10.1371/journal.pone.0196931 Text en © 2018 Germano et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Germano, Antonina
Saba, Laura
De Francia, Silvia
Rapa, Ida
Perotti, Paola
Berruti, Alfredo
Volante, Marco
Terzolo, Massimo
CYP11B1 has no role in mitotane action and metabolism in adrenocortical carcinoma cells
title CYP11B1 has no role in mitotane action and metabolism in adrenocortical carcinoma cells
title_full CYP11B1 has no role in mitotane action and metabolism in adrenocortical carcinoma cells
title_fullStr CYP11B1 has no role in mitotane action and metabolism in adrenocortical carcinoma cells
title_full_unstemmed CYP11B1 has no role in mitotane action and metabolism in adrenocortical carcinoma cells
title_short CYP11B1 has no role in mitotane action and metabolism in adrenocortical carcinoma cells
title_sort cyp11b1 has no role in mitotane action and metabolism in adrenocortical carcinoma cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937768/
https://www.ncbi.nlm.nih.gov/pubmed/29734384
http://dx.doi.org/10.1371/journal.pone.0196931
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