Sorafenib increases cytochrome P450 lipid metabolites in patient with hepatocellular carcinoma

Leineweber, C.G. (Can G.); Rabehl, M. (Miriam); Pietzner, A. (Anne); Rohwer, N. (Nadine); Rothe, M. (Michael); Pech, M. (Maciej); Sangro, B. (Bruno); Verslype, C. (Chris); Basu, B. (Bristi); Sengel, C. (Christian); Ricke, J. (Jeans); Schebb, N.H. (Nils Helge); Weylandt, K.H. (Karsten-H); Benckert, J. (Julia)

Palabras clave :

Hepatocellular carcinoma
Cytochrome P450
Sorafenib
EET
EDP
Omega-3 fatty acids
Oxylipins
Lipidomics

Fecha de publicación :

2023

Versión del Editor:

https://pubmed.ncbi.nlm.nih.gov/36937889/

ISSN :

1663-9812

Nota:

This is an openaccess 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.

Cita:

Leineweber, C. G.; Rabehl, M.; Pietzner, A.; et al. "Sorafenib increases cytochrome P450 lipid metabolites in patient with hepatocellular carcinoma". Frontiers In Pharmacology. 14, 2023, 1124214

Resumen

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.

URI :

https://hdl.handle.net/10171/66202

DOI:

10.3389/fphar.2023.1124214

Aparece en las colecciones:

DA - CUN - Hepatología - Artículos de revista

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