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@ARTICLE{Coronado:908870,
      author       = {Coronado, Mônika Aparecida and de Moraes, Fábio Rogério
                      and Stuqui, Bruna and Calmon, Marília Freitas and Eberle,
                      Raphael Josef and Rahal, Paula and Arni, Raghuvir
                      Krishnaswamy},
      title        = {{T}he {S}ecreted {M}etabolome of {H}ela {C}ells under
                      {E}ffect of {C}rotamine, a {C}ell-{P}enetrating {P}eptide
                      from a {R}attlesnake {U}sing {NMR}-{B}ased {M}etabolomics
                      {A}nalyses},
      journal      = {BioMed},
      volume       = {2},
      number       = {2},
      issn         = {2673-8430},
      address      = {Basel, Switzerland},
      publisher    = {MDPI},
      reportid     = {FZJ-2022-02884},
      pages        = {238 - 254},
      year         = {2022},
      abstract     = {Sequestering and reprogramming of cellular metabolism
                      represents one of the principal hallmarks of several cells.
                      Antimicrobial peptides have been shown to exhibit selective
                      anticancer activities. In this study, the secreted
                      metabolome of HeLa cells under action of the antimicrobial
                      peptide Crotamine from the venom of the South American
                      rattlesnake Crotalus durissus terrificus was evaluated.
                      Crotamine has been shown to be selective for highly
                      proliferating cells and is able to extend the in vivo
                      lifespan. The present study using a cell line of cervical
                      cancer, HeLa cells, provide insights into how Crotamine acts
                      in cell metabolism. NMR spectroscopy was used to identify
                      and quantify relative metabolite levels, which are
                      associated with Crotamine uptake. Statistical analysis
                      reveals that Crotamine dramatically affects metabolites
                      related to glycolysis, metabolism and biosynthesis of amino
                      acids and pyruvate metabolism. The developed machine
                      learning model is found to be robust by ROC curve analysis,
                      suggesting that the metabolic state of HeLa cells treated
                      with Crotamine is different from the control samples. To
                      account for metabolite levels, it is suggested that
                      Crotamine would have to act on glycolysis, which, in turn,
                      affects several other metabolic pathways, such as,
                      glutathione metabolism, TCA cycle and pyruvate metabolism.
                      The observed metabolic changes shed light into the mode of
                      Crotamine function.},
      cin          = {IBI-7},
      ddc          = {610},
      cid          = {I:(DE-Juel1)IBI-7-20200312},
      pnm          = {5241 - Molecular Information Processing in Cellular Systems
                      (POF4-524)},
      pid          = {G:(DE-HGF)POF4-5241},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.3390/biomed2020020},
      url          = {https://juser.fz-juelich.de/record/908870},
}