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Recently, we developed software Isodyn, which extends the methodology of kinetic modeling to the analysis of isotopic isomer distribution for the evaluation of cellular metabolic flux profile under relevant conditions. This tool can be applied to reveal the metabolic effect of proapoptotic drug edelfosine in leukemia Jurkat cell line, uncovering the mechanisms of induction of apoptosis in cancer cells.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The study of <jats:sup>13<\/jats:sup>C distribution of Jukat cells exposed to low edelfosine concentration, which induces apoptosis in \u22645% of cells, revealed metabolic changes previous to the development of apoptotic program. Specifically, it was found that low dose of edelfosine stimulates the TCA cycle. These metabolic perturbations were coupled with an increase of nucleic acid synthesis <jats:italic>de novo<\/jats:italic>, which indicates acceleration of biosynthetic and reparative processes. The further increase of the TCA cycle fluxes, when higher doses of drug applied, eventually enhance reactive oxygen species (ROS) production and trigger apoptotic program.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>The application of Isodyn to the analysis of mechanism of edelfosine-induced apoptosis revealed primary drug-induced metabolic changes, which are important for the subsequent initiation of apoptotic program. Initiation of such metabolic changes could be exploited in anticancer therapy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1752-0509-4-135","type":"journal-article","created":{"date-parts":[[2010,10,6]],"date-time":"2010-10-06T18:15:02Z","timestamp":1286388902000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Edelfosine-induced metabolic changes in cancer cells that precede the overproduction of reactive oxygen species and apoptosis"],"prefix":"10.1186","volume":"4","author":[{"given":"Vitaly A","family":"Selivanov","sequence":"first","affiliation":[]},{"given":"Pedro","family":"Viz\u00e1n","sequence":"additional","affiliation":[]},{"given":"Faustino","family":"Mollinedo","sequence":"additional","affiliation":[]},{"given":"Teresa WM","family":"Fan","sequence":"additional","affiliation":[]},{"given":"Paul WN","family":"Lee","sequence":"additional","affiliation":[]},{"given":"Marta","family":"Cascante","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2010,10,6]]},"reference":[{"key":"546_CR1","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1093\/carcin\/bgp083","volume":"30","author":"P Vizan","year":"2009","unstructured":"Vizan P, Sanchez-Tena S, Alcarraz-Vizan G, Soler M, Messeguer R, Pujol MD, Lee WP, Cascante M: Characterization of the metabolic changes underlying growth factor angiogenic activation: identification of new potential therapeutic targets. 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