Cysteine Restriction in Murine L929 Fibroblasts as an Alternative Strategy to Methionine Restriction in Cancer Therapy

Methionine restriction (MetR) is an efficient method of amino acid restriction (AR) in cells and organisms that induces low energy metabolism (LEM) similar to caloric restriction (CR). The implementation of MetR as a therapy for cancer or other diseases is not simple since the elimination of a singl...

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Autores principales:	Werner Schmitz, Elena Ries, Corinna Koderer, Maximilian Friedrich Völter, Anna Chiara Wünsch, Mohamed El-Mesery, Kyra Frackmann, Alexander Christian Kübler, Christian Linz, Axel Seher
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	methionine restriction cysteine restriction mass spectrometry LC/MS cancer therapy caloric restriction Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/bab2b723715640b5ba9b5810747da43b
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spelling	oai:doaj.org-article:bab2b723715640b5ba9b5810747da43b2021-11-11T17:06:23ZCysteine Restriction in Murine L929 Fibroblasts as an Alternative Strategy to Methionine Restriction in Cancer Therapy10.3390/ijms2221116301422-00671661-6596https://doaj.org/article/bab2b723715640b5ba9b5810747da43b2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11630https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Methionine restriction (MetR) is an efficient method of amino acid restriction (AR) in cells and organisms that induces low energy metabolism (LEM) similar to caloric restriction (CR). The implementation of MetR as a therapy for cancer or other diseases is not simple since the elimination of a single amino acid in the diet is difficult. However, the in vivo turnover rate of cysteine is usually higher than the rate of intake through food. For this reason, every cell can enzymatically synthesize cysteine from methionine, which enables the use of specific enzymatic inhibitors. In this work, we analysed the potential of cysteine restriction (CysR) in the murine cell line L929. This study determined metabolic fingerprints using mass spectrometry (LC/MS). The profiles were compared with profiles created in an earlier work under MetR. The study was supplemented by proliferation studies using D-amino acid analogues and inhibitors of intracellular cysteine synthesis. CysR showed a proliferation inhibition potential comparable to that of MetR. However, the metabolic footprints differed significantly and showed that CysR does not induce classic LEM at the metabolic level. Nevertheless, CysR offers great potential as an alternative for decisive interventions in general and tumour metabolism at the metabolic level.Werner SchmitzElena RiesCorinna KodererMaximilian Friedrich VölterAnna Chiara WünschMohamed El-MeseryKyra FrackmannAlexander Christian KüblerChristian LinzAxel SeherMDPI AGarticlemethionine restrictioncysteine restrictionmass spectrometryLC/MScancer therapycaloric restrictionBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11630, p 11630 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	methionine restriction cysteine restriction mass spectrometry LC/MS cancer therapy caloric restriction Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	methionine restriction cysteine restriction mass spectrometry LC/MS cancer therapy caloric restriction Biology (General) QH301-705.5 Chemistry QD1-999 Werner Schmitz Elena Ries Corinna Koderer Maximilian Friedrich Völter Anna Chiara Wünsch Mohamed El-Mesery Kyra Frackmann Alexander Christian Kübler Christian Linz Axel Seher Cysteine Restriction in Murine L929 Fibroblasts as an Alternative Strategy to Methionine Restriction in Cancer Therapy
description	Methionine restriction (MetR) is an efficient method of amino acid restriction (AR) in cells and organisms that induces low energy metabolism (LEM) similar to caloric restriction (CR). The implementation of MetR as a therapy for cancer or other diseases is not simple since the elimination of a single amino acid in the diet is difficult. However, the in vivo turnover rate of cysteine is usually higher than the rate of intake through food. For this reason, every cell can enzymatically synthesize cysteine from methionine, which enables the use of specific enzymatic inhibitors. In this work, we analysed the potential of cysteine restriction (CysR) in the murine cell line L929. This study determined metabolic fingerprints using mass spectrometry (LC/MS). The profiles were compared with profiles created in an earlier work under MetR. The study was supplemented by proliferation studies using D-amino acid analogues and inhibitors of intracellular cysteine synthesis. CysR showed a proliferation inhibition potential comparable to that of MetR. However, the metabolic footprints differed significantly and showed that CysR does not induce classic LEM at the metabolic level. Nevertheless, CysR offers great potential as an alternative for decisive interventions in general and tumour metabolism at the metabolic level.
format	article
author	Werner Schmitz Elena Ries Corinna Koderer Maximilian Friedrich Völter Anna Chiara Wünsch Mohamed El-Mesery Kyra Frackmann Alexander Christian Kübler Christian Linz Axel Seher
author_facet	Werner Schmitz Elena Ries Corinna Koderer Maximilian Friedrich Völter Anna Chiara Wünsch Mohamed El-Mesery Kyra Frackmann Alexander Christian Kübler Christian Linz Axel Seher
author_sort	Werner Schmitz
title	Cysteine Restriction in Murine L929 Fibroblasts as an Alternative Strategy to Methionine Restriction in Cancer Therapy
title_short	Cysteine Restriction in Murine L929 Fibroblasts as an Alternative Strategy to Methionine Restriction in Cancer Therapy
title_full	Cysteine Restriction in Murine L929 Fibroblasts as an Alternative Strategy to Methionine Restriction in Cancer Therapy
title_fullStr	Cysteine Restriction in Murine L929 Fibroblasts as an Alternative Strategy to Methionine Restriction in Cancer Therapy
title_full_unstemmed	Cysteine Restriction in Murine L929 Fibroblasts as an Alternative Strategy to Methionine Restriction in Cancer Therapy
title_sort	cysteine restriction in murine l929 fibroblasts as an alternative strategy to methionine restriction in cancer therapy
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/bab2b723715640b5ba9b5810747da43b
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Cysteine Restriction in Murine L929 Fibroblasts as an Alternative Strategy to Methionine Restriction in Cancer Therapy

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