%0 Journal Article
%T Identification of metabolites with anticancer properties by computational metabolomics
%A Adrian K Arakaki
%A Roman Mezencev
%A Nathan J Bowen
%A Ying Huang
%A John F McDonald
%A Jeffrey Skolnick
%J Molecular Cancer
%D 2008
%I BioMed Central
%R 10.1186/1476-4598-7-57
%X CoMet, a fully automated Computational Metabolomics method to predict changes in metabolite levels in cancer cells compared to normal references has been developed and applied to Jurkat T leukemia cells with the goal of testing the following hypothesis: Up or down regulation in cancer cells of the expression of genes encoding for metabolic enzymes leads to changes in intracellular metabolite concentrations that contribute to disease progression. All nine metabolites predicted to be lowered in Jurkat cells with respect to lymphoblasts that were examined (riboflavin, tryptamine, 3-sulfino-L-alanine, menaquinone, dehydroepiandrosterone, ¦Á-hydroxystearic acid, hydroxyacetone, seleno-L-methionine and 5,6-dimethylbenzimidazole), exhibited antiproliferative activity that has not been reported before, while only two (bilirubin and androsterone) of the eleven tested metabolites predicted to be increased or unchanged in Jurkat cells displayed significant antiproliferative activity.These results: a) demonstrate that CoMet is a valuable method to identify potential compounds for experimental validation, b) indicate that cancer cell metabolism may be regulated to reduce the intracellular concentration of certain antiproliferative metabolites, leading to uninhibited cellular growth and c) suggest that many other endogenous metabolites with important roles in carcinogenesis are awaiting discovery.Elucidating the metabolic changes exhibited by cancer cells is important not only for diagnostic purposes, but also to more deeply understand the molecular basis of carcinogenesis, which could lead to novel therapeutic approaches. By regulating the expression of oncogenes or modulating various signal transduction systems, it is widely accepted that certain metabolic processes play fundamental roles in cancer progression. The significance of other metabolic phenotypes observed in cancer is more controversial, e.g. the shift in energy production from oxidative phosphorylation (respiration)
%U http://www.molecular-cancer.com/content/7/1/57