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Old 03-29-2018, 07:42 PM
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Default 1H-NMR-based metabolomics approach reveals metabolic mechanism of (-)-5-hydroxy-equol against hepatocellular carcinoma cells in vitro.

1H-NMR-based metabolomics approach reveals metabolic mechanism of (-)-5-hydroxy-equol against hepatocellular carcinoma cells in vitro.

1H-NMR-based metabolomics approach reveals metabolic mechanism of (-)-5-hydroxy-equol against hepatocellular carcinoma cells in vitro.

J Proteome Res. 2018 Mar 28;:

Authors: Gao L, Wang KX, Zhang NN, Li JQ, Qin XM, Wang XL

Abstract
1H-NMR-based metabolomics can rapidly detect metabolic shift under various stimulus, thus it facilitated the dissection of the therapeutic mechanisms of compounds. (-)-5-hydroxy-equol is an isoflavone metabolite that be obtained by microbial biotransformation. In the current work, the effect of (-)-5-hydroxy-equol on hepatocellular carcinoma cells and its mechanism have been explored based on 1H-NMR-based metabolomics approach. Our results revealed that (-)-5-hydroxy-equol can significantly inhibit the proliferation, migration and invasion of SMMC-7721 cells, and inhibit the proliferation of HepG2 cells. Metabolomics revealed that 17 differential metabolites involving in amino acid metabolism and energy metabolism were significantly changed inside and outside of the cells after treatment of (-)-5-hydroxy-equol. Specifically, (-)-5-hydroxy-equol at concentration of 30 ?M significantly decreased the concentrations of pyruvate, glutamate and glucose. As glycometabolism is a crucial feature of cancer-specific metabolism, we further verified enzymes and proteins that closely relevant to glycometabolism. Our results indicated that (-)-5-hydroxy-equol modulated glycolysis in HCC through inhibition of activities of hexokinase, phosphofructokinase and pyruvate kinase, and the expression of pyruvate kinase M2. This study revealed that metabolomic analysis integrating with further verifications at the biochemical level can facilitate understanding the anti-HCC mechanisms of (-)-5-hydroxy-equol.


PMID: 29589762 [PubMed - as supplied by publisher]



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