Tuyển tập các báo cáo nghiên cứu về hóa học được đăng trên tạp chí sinh học đề tài : The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate, iodoacetate or 5-fluorouracil | Sánchez-Aragó and Cuezva Journal of Translational Medicine 2011 9 19 http content 9 1 19 TRANSLATIONAL MEDICINE RESEARCH Open Access The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate iodoacetate or 5-fluorouracil María Sánchez-Aragó José M Cuezva Abstract Background Metabolic reprogramming resulting in enhanced glycolysis is a phenotypic trait of cancer cells which is imposed by the tumor microenvironment and is linked to the down-regulation of the catalytic subunit of the mitochondrial H -ATPase b-F1-ATPase . The bioenergetic signature is a protein ratio b-F1-ATPase GAPDH which provides an estimate of glucose metabolism in tumors and serves as a prognostic indicator for cancer patients. Targeting energetic metabolism could be a viable alternative to conventional anticancer chemotherapies. Herein we document that the bioenergetic signature of isogenic colon cancer cells provides a gauge to predict the cell-death response to the metabolic inhibitors 3-bromopyruvate 3BrP and iodoacetate IA and the anti-metabolite 5-fluorouracil 5-FU . Methods The bioenergetic signature of the cells was determined by western blotting. Aerobic glycolysis was determined from lactate production rates. The cell death was analyzed by fluorescence microscopy and flow cytometry. Cellular ATP concentrations were determined using bioluminiscence. Pearson s correlation coefficient was applied to assess the relationship between the bioenergetic signature and the cell death response. In vivo tumor regression activities of the compounds were assessed using a xenograft mouse model injected with the highly glycolytic HCT116 colocarcinoma cells. Results We demonstrate that the bioenergetic signature of isogenic HCT116 cancer cells inversely correlates with the potential to execute necrosis in response to 3BrP or IA treatment. Conversely the bioenergetic signature directly correlates with the .
