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Heterogeneity in tumor cell energetic metabolome at different cell cycle phases of human colon cancer cell lines

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Abstract

In this present study, the efficacy of metabolomics as a tool for tumor cell energetics for in vitro cell cultures was demonstrated with full competence for the first time by elucidating the anabolic and energy-yielding segments of glycolysis and glutaminolysis, which constitute a part of energy metabolism in tumor cells. By synchronizing colon cancer cells SW480 and SW620 in culture, the metabolome specific to cell cycle phases was analyzed using nuclear magnetic resonance spectroscopy. At the G1/S transition of the cell cycle (i.e. transition from cell growth to duplication of genetic material), the majority of the energy production was realized by glycolysis through a high channeling of glucose carbons towards lactate. During the late S phase, the majority of energy was produced by glutaminolysis through a high channeling of glutamine carbons towards lactate, while the glucose carbons were channeled towards bio-synthetic pathways. These results indicate that the metabolism of proliferating cells is heterogeneous throughout the cell cycle and can be better interpreted on the basis of different cell cycle phases. These findings could be exploited for the development of a tool for tumor diagnosis as well as for targeting tumors.

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Acknowledgments

The financial support from the Ministerium für Innovation, Wissenschaft, Forschung und Technologie des Landes Nordrhein-Westfalen; Bundesministerium für Bildung und Forschung (Pakt für Forschung und Innovation, dem gemeinsamen Förderungsprogramm von Bund und Ländern) is greatly acknowledged. The author is also thankful to EU-NMR-Centre in Birmingham and Ulrich Günther for the NMR measurements and to Jorg Lambert and Roland Hergenröder for their fruitful discussions at ISAS-Institute for Analytical Sciences.

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Authors and Affiliations

  1. Department of Microfluidics and Clinical Diagonstics, KIST Europe—Korea Institute of Science and Technology, Campus E7 1, 66123, Saarbrücken, Germany

    Sasidhar Maddula & Jörg Ingo Baumbach

  2. ISAS-Institute for Analytical Sciences, Bunsen-Kirchhoff-Str. 11, 44139, Dortmund, Germany

    Sasidhar Maddula & Jörg Ingo Baumbach

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  1. Sasidhar Maddula
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Correspondence to Sasidhar Maddula.

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Fig. SI-1

Comparison of asynchronous and synchronous samples of SW480 cells. Fold change pattern of 61 metabolites, containing 51 significantly (p < 0.01) regulated metabolites. Asynchronous (white), G1/S transition phase (light gray), S phase (gray) and G2/M transition phase (black – not relevant to this paper) (PNG 89 kb) (PNG 90 kb)

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Maddula, S., Baumbach, J.I. Heterogeneity in tumor cell energetic metabolome at different cell cycle phases of human colon cancer cell lines. Metabolomics 7, 509–523 (2011). https://doi.org/10.1007/s11306-010-0267-y

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