Abstract
Metabolomics technologies continue to develop not only to study endpoint steady-state concentrations of numerous metabolites in normal and cancer cells but also to examine metabolic flux and networks. These techniques are of importance for understanding tumor cell metabolism and for the development of new drugs and treatment strategies. The choice of tracer substrates is central as 13C-labeled substrates readily improve real-time reaction visibility by increasing metabolic network transparencies in cancer metabolomics. In this chapter, targeted [1,2- 13C2]-d-glucose single tracer fate associations are compared with the external [U- 13C18]-stearate oxidation model for thiazolidinedione efficacy testing in primary liver tumor cells. Although the externally supplied [U- 13C18]-stearate tracer readily labels multiple products by acetyl-CoA exchange, parallel stearate synthesis and mobilization from unlabeled intracellular pools disrupt its uptake after drug treatment. This can be overcome by using cross-labeled 13C-stearate from [1,2- 13C2]-d-glucose as the internal tracer and the independent explanatory variable to study associations among markers of rosiglitazone-induced stearate breakdown in a single [1,2- 13C2]-d-glucose tracer experiment during drug efficacy testing in cultured cells.
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Acknowledgments
Isotopolome-wide mathematical fitting of GC-MS data involving 13C-glucose with 13C-stearate to product processing was supported by the Hirshberg Foundation for Pancreatic Cancer Research and the UCLA Clinical and Translational Science Institute (UL1TR000124) to LGB and EJM. Targeted 13C tracer drug efficacy marker data diagnostics for cancer were partially supported by the European Regional Development Fund, Central Hungary Operative Program, and New Széchenyi Plan (KMOP-1.1.4-11/A-2011-01-05) to GS. We thank Eszter Boros and Ferenc Nádudvari for their technical help in registering additional 13C tracer presentation by LGB on the World Wide Web at http://youtu.be/GkYAjabGxJs regarding mammalian cell mitochondria.
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The authors declare no conflict of financial interest.
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Boros, L.G. et al. (2015). Targeted 13C-Labeled Tracer Fate Associations for Drug Efficacy Testing in Cancer. In: Mazurek, S., Shoshan, M. (eds) Tumor Cell Metabolism. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1824-5_15
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DOI: https://doi.org/10.1007/978-3-7091-1824-5_15
Publisher Name: Springer, Vienna
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