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(447e) Integrated Energetics and Flux Analysis Reveals Differential Metabolic Reprogramming in Cancer Cells

Nagrath, D., Rice University
Achreja, A., Rice University
Yang, L., Rice University

Cancer cell metabolism was investigated using systems biology tools such as metabolic flux analysis (MFA) to reveal intracellular cancer cell metabolic flux distribution. To obtain a complete role of nutrient-induced deprivation in metabolic reprogramming of cancer cells, we need to use metabolic flux analysis to determine unknown intracellular fluxes.  Here, we have developed an integrated energy balance and flux balance analysis framework for analyzing cancer cell metabolism. Our framework allows estimation of intracellular fluxes and reveals specific adaptations and dysregulation of metabolic pathways in ovarian cancer cells as a result of the nutrient deprivation conditions.  Our findings indicate that NAD+/NADH ratio regulates glutamine’s direct effect on lactate production irrespective of the bioenergetic substrate requirement for different kinds of cancer cells. Our findings, using quantification of metabolites pertaining to central carbon and nitrogen metabolism provided clues as to which pathways relevant to glycolysis, the pentose phosphate pathway, the TCA, urea cycles and lipid cycles, amino acid and nucleotide metabolisms may be altered by nutrients in cancer cells. This resulted in identification of dominant factors which control cancer metabolism. We believe that development of our oncosecretomics based metabolic strategy provides an unprecedented opportunity for the development of nutritional supplementation that can deregulate the adaptations and alterations induced by various nutrients in cancer metabolism.