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Identification of biomarkers for apoptosis in cancer cell lines using metabolomics: tools for individualized medicine
Author(s) -
Halama A.,
Riesen N.,
Möller G.,
Hrabě de Angelis M.,
Adamski J.
Publication year - 2013
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12117
Subject(s) - metabolomics , apoptosis , staurosporine , metabolite , medicine , metabolome , etoposide , cancer research , pharmacology , computational biology , biochemistry , bioinformatics , biology , chemotherapy , signal transduction , protein kinase c
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 H ep G 2 and HEK 293 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 H ep G 2 and HEK 293 cells irrespective of the apoptosis inducer. Conclusion Our observations clearly indicate the potential of metabolomics in detecting metabolic biomarkers applicable in theranostics and for monitoring drug efficacy.