Differential changes in purine nucleotides after Doxorubicin treatment of human cancer cells in vitro

  • Authors:
    • Stefan Walenta
    • Barbara Feigk
    • Ines Wachsmuth
    • Torsten Dunkern
    • Hadassa Degani
    • Wolfgang Mueller-Klieser
  • View Affiliations

  • Published online on: August 1, 2002     https://doi.org/10.3892/ijo.21.2.289
  • Pages: 289-296
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Abstract

The present investigation was performed to elucidate the role of purine nucleotides as potential indicators of chemosensitivity of malignant tumors. Drug-sensitive (s) and -resistant (r) tumor cell lines grown as monolayers (s: T47D, MCF-7 wild-type; r: NCI/ADR-RES, MCF-7/MDR) or as multicellular spheroids (T47D; NCI/ADR-RES) were exposed to 0.1, 1.0, and 10.0 μM Doxorubicin for up to 24 h. Purine nucleotides were assayed using HPLC and with some selected spheroids using imaging bioluminescence. The data show that in the time frame of the experiments reproducible and statistically significant changes in the nucleotides only occur at the highest drug concentration investigated. Under these conditions and using monolayer cultures, Doxorubicin caused a significant increase in ATP and GTP in sensitive but not in resistant cancer cells. Consequently, this differential change may be exploited for drug sensitivity testing in vitro. Doxorubicin exposure to spheroids was associated with significant increases in ATP and GTP in both sensitive and resistant variants. However, the kinetic of the changes in GTP was largely different between T47D and NCI/ADR-RES spheroids with a long-lasting, almost 3-fold elevation and a smaller, relatively short transient increase in GTP, respectively. Supplementing experiments with Doxorubicin treatment under inhibition of oxidative phosphorylation with Oligomycin abolished the drug-induced ATP and GTP peaks at persistent increases in ADP and AMP. Assuming that the spheroids may represent the in vivo situation to a better degree than monolayer cultures, experimental in vivo studies should clarify whether kinetic changes in GTP could be used as differential markers for the chemosensitivity of solid tumors. The experiments using Oligomycin support the hypothesis that purine nucleotides may be recycled from DNA fragments that result from the interaction of the drug with the DNA strands.

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August 2002
Volume 21 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Walenta S, Feigk B, Wachsmuth I, Dunkern T, Degani H and Mueller-Klieser W: Differential changes in purine nucleotides after Doxorubicin treatment of human cancer cells in vitro. Int J Oncol 21: 289-296, 2002
APA
Walenta, S., Feigk, B., Wachsmuth, I., Dunkern, T., Degani, H., & Mueller-Klieser, W. (2002). Differential changes in purine nucleotides after Doxorubicin treatment of human cancer cells in vitro. International Journal of Oncology, 21, 289-296. https://doi.org/10.3892/ijo.21.2.289
MLA
Walenta, S., Feigk, B., Wachsmuth, I., Dunkern, T., Degani, H., Mueller-Klieser, W."Differential changes in purine nucleotides after Doxorubicin treatment of human cancer cells in vitro". International Journal of Oncology 21.2 (2002): 289-296.
Chicago
Walenta, S., Feigk, B., Wachsmuth, I., Dunkern, T., Degani, H., Mueller-Klieser, W."Differential changes in purine nucleotides after Doxorubicin treatment of human cancer cells in vitro". International Journal of Oncology 21, no. 2 (2002): 289-296. https://doi.org/10.3892/ijo.21.2.289