Cell cycle phase specific metabolism of colon cancer cells: a metabolome study

Discrimination of healthy from cancerous cells is of major interest in fundamental research and in the health industry. In this doctoral thesis, metabolomics was exploited as a tool for monitoring tumor cell metabolism, with the ultimate aim of identifying metabolic differences for the discrimination of healthy from cancerous cells. Tumor cell metabolism is often characterized by high glycolytic and glutaminolytic capacities (i.e., high flux). The main question that was worked on in this thesis was: Is the composition and/or concentration of the metabolome of cancer cells dependent on the cell cycle? The metabolome of synchronized colon cancer cells was analyzed using two orthogonal analytical methods-namely, nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. At the G1/S transition and late S phase of the cell cycle, various metabolite concentrations differed significantly, independent of cell line used. The concentrations of D-glyceraldehyde 3-phosphate, phosphoenolpyruvate, and acetate in the G1/S transition phase were significantly higher when compared to the S phase and in asynchronous samples. Additionally, the concentration of lactate was considerably higher in both synchronous cultures compared to the asynchronous culture. Furthermore, the concentrations of glutamate, ketoglutarate, and succinate in both G1/S transition phase and S phase of synchronous cells were found to vary significantly compared to the asynchronous cells. The results from this doctoral study indicate that operation of cellular metabolism varies throughout the cell cycle, most likely to fulfill the changing demands of growth, genetic material duplication and resting.