ISOTOPE-ASSISTED METABOLIC FLUX ANALYSIS IN THE INVESTIGATION OF PROSTATE CANCER
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Understanding cancer metabolism is critical to developing treatment strategies which selectively target malignant cells. Toward this objective, we apply isotope-assisted metabolic flux analysis to the investigation of prostate cancer, which kills over 28,000 men every year in the United States alone. We performed metabolic flux analysis (MFA) on immortal prostate cancer cell lines to determine the relative activity of metabolic pathways that constitute central carbon metabolism. We identified multiple deviations of the malignant phenotype from that of benign cells. We found that all cell lines exhibited a preference for the pentose phosphate pathway over glycolysis for glucose catabolism, with an average flux partition of 53% ± 25% in favor of the pentose phosphate pathway. We also identified a drop in TCA cycle flux from 33.5 ± 10.5 for LNCaP to 19.7 ± 7.8 for CSS90 cells, possibly indicating a preference for glutaminolysis and lipogenesis to fuel rapid proliferation.