title: Identification of biomarkers for apoptosis in cancer cell lines using metabolomics: tools for individualized medicine.
abstract: BACKGROUND
  Metabolomics is a versatile unbiased method to search for biomarkers of human disease. In particular, one approach in cancer therapy is to promote apoptosis in tumour cells; this could be improved with specific biomarkers of apoptosis for monitoring treatment. We recently observed specific metabolic patterns in apoptotic cell lines; however, in that study, apoptosis was only induced with one pro-apoptotic agent, staurosporine.
  
  
  OBJECTIVE
  The aim of this study was to find novel biomarkers of apoptosis by verifying our previous findings using two further pro-apoptotic agents, 5-fluorouracil and etoposide, that are commonly used in anticancer treatment.
  
  
  METHODS
  Metabolic parameters were assessed in HepG2 and HEK293 cells using the newborn screening assay adapted for cell culture approaches, quantifying the levels of amino acids and acylcarnitines with mass spectrometry.
  
  
  RESULTS
  We were able to identify apoptosis-specific changes in the metabolite profile. Moreover, the amino acids alanine and glutamate were both significantly up-regulated in apoptotic HepG2 and HEK293 cells irrespective of the apoptosis inducer.
  
  
  CONCLUSIONS
  Our observations clearly indicate the potential of metabolomics in detecting metabolic biomarkers applicable in theranostics and for monitoring drug efficacy.
authors.affiliation: Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics, Genome Analysis Center, Neuherberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Halama
authors.forename: N
authors.initials: N
authors.lastname: Riesen
authors.forename: G
authors.initials: G
authors.lastname: Möller
authors.forename: M
authors.initials: M
authors.lastname: Hrabě de Angelis
authors.forename: J
authors.initials: J
authors.lastname: Adamski
mesh_terms: D000409:Alanine / Q000032:analysis; D000596:Amino Acids / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D002331:Carnitine / Q000031:analogs & derivatives / Q000032:analysis; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D005047:Etoposide / Q000494:pharmacology; D017022:Flow Injection Analysis; D005472:Fluorouracil / Q000494:pharmacology; D018698:Glutamic Acid / Q000032:analysis; D057809:HEK293 Cells / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D056945:Hep G2 Cells / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D055432:Metabolomics / Q000379:methods; D057285:Precision Medicine / Q000379:methods*
chemical_list: D000596:Amino Acids; D015415:Biomarkers; C116917:acylcarnitine; D018698:Glutamic Acid; D005047:Etoposide; D053148:Caspase 3; D053179:Caspase 7; D000409:Alanine; D002331:Carnitine; D005472:Fluorouracil
keywords: apoptosis; biomarkers; cancer; mass spectrometry; metabolomics