Molecular Biology Reports

, Volume 29, Issue 1, pp 7–12

Metabolic Control Analysis Aimed at the Ribose Synthesis Pathways of Tumor Cells: A New Strategy for Antitumor Drug Development

Authors

  • Joan Boren
    • Department of Biochemistry and Molecular BiologyUniversity of Barcelona
  • Antonio Ramos Montoya
    • Department of Biochemistry and Molecular BiologyUniversity of Barcelona
  • Pedro de Atauri
    • Department of Biochemistry and Molecular BiologyUniversity of Barcelona
  • Begoña Comin-Anduix
    • Department of Biochemistry and Molecular BiologyUniversity of Barcelona
  • Antonio Cortes
    • Department of Biochemistry and Molecular BiologyUniversity of Barcelona
  • Josep J. Centelles
    • Department of Biochemistry and Molecular BiologyUniversity of Barcelona
  • Wilma M. Frederiks
    • Department of Cell Biology and HistologyUniversity of Amsterdam, Academical Medical Centre
  • Cornelis J.F. Van Noorden
    • Department of Cell Biology and HistologyUniversity of Amsterdam, Academical Medical Centre
  • Marta Cascante
    • Department of Biochemistry and Molecular BiologyUniversity of Barcelona
Article

DOI: 10.1023/A:1020333730485

Cite this article as:
Boren, J., Montoya, A.R., de Atauri, P. et al. Mol Biol Rep (2002) 29: 7. doi:10.1023/A:1020333730485

Abstract

Metabolic control analysis predicts that effects on tumor growth are likely to be obtained with lower concentrations of drug, if an enzyme with a high control coefficient on tumor growth is being inhibited. Here we measure glucose-6-phosphate dehydrogenase (G6PDH) control coefficient on in vivo tumor growth using mice bearing Ehrlich ascites tumor cells. We used dehydroepiandrosterone-sulphate (DHEA-S), an uncompetitive inhibitor of this enzyme and the in situ cytochemical method to measure the enzyme activity changes that accompany changes on tumor cell growth. This method ensures that the enzyme activity determined is the one existing in the in situ conditions and enables computing a control coefficient in in situ conditions. From the data obtained on tumor cell number and the in situ enzyme activities in absence and presence of DHEA-S, a control coefficient of 0.41 for G6PDH on tumor cell growth was computed. This value is approximately the half of the transketolase control coefficient value of 0.9 previously reported. Moreover, the use of in situ methods to assess enzyme activities, applied for first time for the calculation of control coefficients in this study, opens new avenues to the use of uncompetitive inhibitors for the measurement of in situ control coefficients.

dehydroepiandrosterone-sulphateflux control coefficientsglucose-6-phophate dehydrogenaseribose synthesistumor cell proliferation

Copyright information

© Kluwer Academic Publishers 2002