Metabolic reprogramming by folate restriction leads to a less aggressive cancer phenotype

摘要: Folate coenzymes are involved in biochemical reactions of one-carbon transfer, and deficiency this vitamin impairs cellular proliferation, migration survival many cell types. Here the effect folate restriction on mammary cancer was evaluated using three distinct breast subtypes differing their aggressiveness metastatic potential: non-invasive basal-like (E-Wnt), invasive but minimally claudin-low (M-Wnt), highly (metM-Wntliver) lines, each derived from same pool MMTV-Wnt-1 transgenic mouse tumors. NMR-based metabolomics used to quantitate 41 major metabolites cells grown folate-free medium versus standard medium. Each line demonstrated metabolic reprogramming when In E-Wnt, M-Wnt metM-Wntliver 12, 29, 25 metabolites, respectively, were significantly different (p<0.05 at least 1.5-fold change). The levels eight (aspartate, ATP, creatine, creatine phosphate, formate, serine, taurine beta-alanine) changed folate-restricted line. Increased glucose, decreased lactate, inhibition glycolysis, invasion occurred (but not E-Wnt cells) These effects accompanied by altered several folate-metabolizing enzymes, indicating that observed may result both availability metabolism. findings reveal results bioenergetic changes a less aggressive phenotype. Implications: Metabolic driven represents therapeutic target for reducing burden cancer.