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

International Journal of Molecular Sciences

Werner Schmitz¹  Mohamed El-Mesery²  Maximilian Friedrich Völter³  Kyra Frackmann³  Corinna Koderer³  Anna Chiara Wünsch³  Alexander Christian Kübler³  Christian Linz³  Elena Ries³  Axel Seher³ 

[1] Department of Biochemistry and Molecular Biology, Biocenter, D-97074 Wuerzburg, Germany;Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt;Department of Oral and Maxillofacial Plastic Surgery, University Hospital Wuerzburg, D-97070 Wuerzburg, Germany;

关键词: methionine restriction;    cysteine restriction;    mass spectrometry;    LC/MS;    cancer therapy;    caloric restriction;   

DOI  :  10.3390/ijms222111630

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown