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Sorafenib increases cytochrome P450 lipid metabolites in patient with hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is a leading cause of cancer death, and medical treatment options are limited. The multikinase inhibitor sorafenib was the first approved drug widely used for systemic therapy in advanced HCC. Sorafenib might affect polyunsaturated fatty acids (PUFA)-derived epoxygenat...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10020374/ https://www.ncbi.nlm.nih.gov/pubmed/36937889 http://dx.doi.org/10.3389/fphar.2023.1124214 |
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author | Leineweber, Can G. Rabehl, Miriam Pietzner, Anne Rohwer, Nadine Rothe, Michael Pech, Maciej Sangro, Bruno Sharma, Rohini Verslype, Chris Basu, Bristi Sengel, Christian Ricke, Jens Schebb, Nils Helge Weylandt, Karsten-H. Benckert, Julia |
author_facet | Leineweber, Can G. Rabehl, Miriam Pietzner, Anne Rohwer, Nadine Rothe, Michael Pech, Maciej Sangro, Bruno Sharma, Rohini Verslype, Chris Basu, Bristi Sengel, Christian Ricke, Jens Schebb, Nils Helge Weylandt, Karsten-H. Benckert, Julia |
author_sort | Leineweber, Can G. |
collection | PubMed |
description | Hepatocellular carcinoma (HCC) is a leading cause of cancer death, and medical treatment options are limited. The multikinase inhibitor sorafenib was the first approved drug widely used for systemic therapy in advanced HCC. Sorafenib might affect polyunsaturated fatty acids (PUFA)-derived epoxygenated metabolite levels, as it is also a potent inhibitor of the soluble epoxide hydrolase (sEH), which catalyzes the conversion of cytochrome-P450 (CYP)-derived epoxide metabolites derived from PUFA, such as omega-6 arachidonic acid (AA) and omega-3 docosahexaenoic acid (DHA), into their corresponding dihydroxy metabolites. Experimental studies with AA-derived epoxyeicosatrienoic acids (EETs) have shown that they can promote tumor growth and metastasis, while DHA-derived 19,20-epoxydocosapentaenoic acid (19,20-EDP) was shown to have anti-tumor activity in mice. In this study, we found a significant increase in EET levels in 43 HCC patients treated with sorafenib and a trend towards increased levels of DHA-derived 19,20-EDP. We demonstrate that the effect of sorafenib on CYP- metabolites led to an increase of 19,20-EDP and its dihydroxy metabolite, whereas DHA plasma levels decreased under sorafenib treatment. These data indicate that specific supplementation with DHA could be used to increase levels of the epoxy compound 19,20-EDP with potential anti-tumor activity in HCC patients receiving sorafenib therapy. |
format | Online Article Text |
id | pubmed-10020374 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100203742023-03-18 Sorafenib increases cytochrome P450 lipid metabolites in patient with hepatocellular carcinoma Leineweber, Can G. Rabehl, Miriam Pietzner, Anne Rohwer, Nadine Rothe, Michael Pech, Maciej Sangro, Bruno Sharma, Rohini Verslype, Chris Basu, Bristi Sengel, Christian Ricke, Jens Schebb, Nils Helge Weylandt, Karsten-H. Benckert, Julia Front Pharmacol Pharmacology Hepatocellular carcinoma (HCC) is a leading cause of cancer death, and medical treatment options are limited. The multikinase inhibitor sorafenib was the first approved drug widely used for systemic therapy in advanced HCC. Sorafenib might affect polyunsaturated fatty acids (PUFA)-derived epoxygenated metabolite levels, as it is also a potent inhibitor of the soluble epoxide hydrolase (sEH), which catalyzes the conversion of cytochrome-P450 (CYP)-derived epoxide metabolites derived from PUFA, such as omega-6 arachidonic acid (AA) and omega-3 docosahexaenoic acid (DHA), into their corresponding dihydroxy metabolites. Experimental studies with AA-derived epoxyeicosatrienoic acids (EETs) have shown that they can promote tumor growth and metastasis, while DHA-derived 19,20-epoxydocosapentaenoic acid (19,20-EDP) was shown to have anti-tumor activity in mice. In this study, we found a significant increase in EET levels in 43 HCC patients treated with sorafenib and a trend towards increased levels of DHA-derived 19,20-EDP. We demonstrate that the effect of sorafenib on CYP- metabolites led to an increase of 19,20-EDP and its dihydroxy metabolite, whereas DHA plasma levels decreased under sorafenib treatment. These data indicate that specific supplementation with DHA could be used to increase levels of the epoxy compound 19,20-EDP with potential anti-tumor activity in HCC patients receiving sorafenib therapy. Frontiers Media S.A. 2023-03-03 /pmc/articles/PMC10020374/ /pubmed/36937889 http://dx.doi.org/10.3389/fphar.2023.1124214 Text en Copyright © 2023 Leineweber, Rabehl, Pietzner, Rohwer, Rothe, Pech, Sangro, Sharma, Verslype, Basu, Sengel, Ricke, Schebb, Weylandt and Benckert. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Leineweber, Can G. Rabehl, Miriam Pietzner, Anne Rohwer, Nadine Rothe, Michael Pech, Maciej Sangro, Bruno Sharma, Rohini Verslype, Chris Basu, Bristi Sengel, Christian Ricke, Jens Schebb, Nils Helge Weylandt, Karsten-H. Benckert, Julia Sorafenib increases cytochrome P450 lipid metabolites in patient with hepatocellular carcinoma |
title | Sorafenib increases cytochrome P450 lipid metabolites in patient with hepatocellular carcinoma |
title_full | Sorafenib increases cytochrome P450 lipid metabolites in patient with hepatocellular carcinoma |
title_fullStr | Sorafenib increases cytochrome P450 lipid metabolites in patient with hepatocellular carcinoma |
title_full_unstemmed | Sorafenib increases cytochrome P450 lipid metabolites in patient with hepatocellular carcinoma |
title_short | Sorafenib increases cytochrome P450 lipid metabolites in patient with hepatocellular carcinoma |
title_sort | sorafenib increases cytochrome p450 lipid metabolites in patient with hepatocellular carcinoma |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10020374/ https://www.ncbi.nlm.nih.gov/pubmed/36937889 http://dx.doi.org/10.3389/fphar.2023.1124214 |
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