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Cysteine restriction in murine L929 fibroblasts as an alternative strategy to methionine restriction in cancer therapy
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-265486
- 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 ofMethionine 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.…
Autor(en): | Werner SchmitzORCiD, Elena Ries, Corinna Koderer, Maximilian Friedrich Völter, Anna Chiara Wünsch, Mohamed El-Mesery, Kyra Frackmann, Alexander Christian Kübler, Christian Linz, Axel SeherORCiD |
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URN: | urn:nbn:de:bvb:20-opus-265486 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Theodor-Boveri-Institut für Biowissenschaften |
Medizinische Fakultät / Klinik und Poliklinik für Mund-, Kiefer- und Plastische Gesichtschirurgie | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | International Journal of Molecular Sciences |
ISSN: | 1422-0067 |
Erscheinungsjahr: | 2021 |
Band / Jahrgang: | 22 |
Heft / Ausgabe: | 21 |
Aufsatznummer: | 11630 |
Originalveröffentlichung / Quelle: | International Journal of Molecular Sciences (2021) 22:21, 11630. https://doi.org/10.3390/ijms222111630 |
DOI: | https://doi.org/10.3390/ijms222111630 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | LC/MS; amino acid analogues; caloric restriction; cancer therapy; cysteine restriction; cysteine synthase inhibitor; homocysteine; mass spectrometry; methionine restriction |
Datum der Freischaltung: | 29.04.2022 |
Open-Access-Publikationsfonds / Förderzeitraum 2021 | |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |