Data from Energy Management by Enhanced Glycolysis in G<sub>1</sub>-phase in Human Colon Cancer Cells <i>In Vitro</i> and <i>In Vivo</i>

Abstract

<div>Abstract<p>Activation of aerobic glycolysis in cancer cells is well known as the Warburg effect, although its relation to cell- cycle progression remains unknown. In this study, human colon cancer cells were labeled with a cell-cycle phase-dependent fluorescent marker Fucci to distinguish cells in G<sub>1</sub>-phase and those in S + G<sub>2</sub>/M phases. Fucci-labeled cells served as splenic xenograft transplants in super-immunodeficient NOG mice and exhibited multiple metastases in the livers, frozen sections of which were analyzed by semiquantitative microscopic imaging mass spectrometry. Results showed that cells in G<sub>1</sub>-phase exhibited higher concentrations of ATP, NADH, and UDP-N-acetylglucosamine than those in S and G<sub>2</sub>–M phases, suggesting accelerated glycolysis in G<sub>1</sub>-phase cells <i>in vivo</i>. Quantitative determination of metabolites in cells synchronized in S, G<sub>2</sub>–M, and G<sub>1</sub> phases suggested that efflux of lactate was elevated significantly in G<sub>1</sub>-phase. By contrast, ATP production in G<sub>2</sub>–M was highly dependent on mitochondrial respiration, whereas cells in S-phase mostly exhibited an intermediary energy metabolism between G<sub>1</sub> and G<sub>2</sub>–M phases. Isogenic cells carrying a p53-null mutation appeared more active in glycolysis throughout the cell cycle than wild-type cells. Thus, as the cell cycle progressed from G<sub>2</sub>–M to G<sub>1</sub> phases, the dependency of energy production on glycolysis was increased while the mitochondrial energy production was reciprocally decreased.</p><p><b>Implications:</b> These results shed light on distinct features of the phase-specific phenotypes of metabolic systems in cancer cells. <i>Mol Cancer Res; 11(9); 973–85. ©2013 AACR</i>.</p></div>