The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate, iodoacetate or 5-fluorouracil
<p>Abstract</p> <p>Background</p> <p>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<su...
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| Format: | Article |
| Language: | English |
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BMC
2011-02-01
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| Series: | Journal of Translational Medicine |
| Online Access: | http://www.translational-medicine.com/content/9/1/19 |
| _version_ | 1811320470707896320 |
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| author | Cuezva José M Sánchez-Aragó María |
| author_facet | Cuezva José M Sánchez-Aragó María |
| author_sort | Cuezva José M |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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<sup>+</sup>-ATPase (β-F1-ATPase). The <it>bioenergetic signature </it>is a protein ratio (β-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 <it>bioenergetic signature </it>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).</p> <p>Methods</p> <p>The <it>bioenergetic signature </it>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 <it>bioenergetic signature </it>and the cell death response. <it>In vivo </it>tumor regression activities of the compounds were assessed using a xenograft mouse model injected with the highly glycolytic HCT116 colocarcinoma cells.</p> <p>Results</p> <p>We demonstrate that the <it>bioenergetic signature </it>of isogenic HCT116 cancer cells inversely correlates with the potential to execute necrosis in response to 3BrP or IA treatment. Conversely, the <it>bioenergetic signature </it>directly correlates with the potential to execute apoptosis in response to 5-FU treatment in the same cells. However, despite the large differences observed in the <it>in vitro </it>cell-death responses associated with 3BrP, IA and 5-FU, the <it>in vivo </it>tumor regression activities of these agents were comparable.</p> <p>Conclusions</p> <p>Overall, we suggest that the determination of the <it>bioenergetic signature </it>of colon carcinomas could provide a tool for predicting the therapeutic response to various chemotherapeutic strategies aimed at combating tumor progression.</p> |
| first_indexed | 2024-04-13T12:59:52Z |
| format | Article |
| id | doaj.art-c4c0eb3c81f241bbaa42a07f2a647105 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-13T12:59:52Z |
| publishDate | 2011-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-c4c0eb3c81f241bbaa42a07f2a6471052022-12-22T02:45:57ZengBMCJournal of Translational Medicine1479-58762011-02-01911910.1186/1479-5876-9-19The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate, iodoacetate or 5-fluorouracilCuezva José MSánchez-Aragó María<p>Abstract</p> <p>Background</p> <p>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<sup>+</sup>-ATPase (β-F1-ATPase). The <it>bioenergetic signature </it>is a protein ratio (β-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 <it>bioenergetic signature </it>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).</p> <p>Methods</p> <p>The <it>bioenergetic signature </it>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 <it>bioenergetic signature </it>and the cell death response. <it>In vivo </it>tumor regression activities of the compounds were assessed using a xenograft mouse model injected with the highly glycolytic HCT116 colocarcinoma cells.</p> <p>Results</p> <p>We demonstrate that the <it>bioenergetic signature </it>of isogenic HCT116 cancer cells inversely correlates with the potential to execute necrosis in response to 3BrP or IA treatment. Conversely, the <it>bioenergetic signature </it>directly correlates with the potential to execute apoptosis in response to 5-FU treatment in the same cells. However, despite the large differences observed in the <it>in vitro </it>cell-death responses associated with 3BrP, IA and 5-FU, the <it>in vivo </it>tumor regression activities of these agents were comparable.</p> <p>Conclusions</p> <p>Overall, we suggest that the determination of the <it>bioenergetic signature </it>of colon carcinomas could provide a tool for predicting the therapeutic response to various chemotherapeutic strategies aimed at combating tumor progression.</p>http://www.translational-medicine.com/content/9/1/19 |
| spellingShingle | Cuezva José M Sánchez-Aragó María The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate, iodoacetate or 5-fluorouracil Journal of Translational Medicine |
| title | The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate, iodoacetate or 5-fluorouracil |
| title_full | The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate, iodoacetate or 5-fluorouracil |
| title_fullStr | The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate, iodoacetate or 5-fluorouracil |
| title_full_unstemmed | The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate, iodoacetate or 5-fluorouracil |
| title_short | The bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3-bromopyruvate, iodoacetate or 5-fluorouracil |
| title_sort | bioenergetic signature of isogenic colon cancer cells predicts the cell death response to treatment with 3 bromopyruvate iodoacetate or 5 fluorouracil |
| url | http://www.translational-medicine.com/content/9/1/19 |
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