Early changes in metabolism of leukemic cell lines upon induction of apoptosis by cytotoxic drugs

Sangeeta Khare, Yona Banai, Kuppan Gokulan, Roger Smith, Darwin S. Linthicum, Jaime F. Modiano

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

We evaluated real-time changes in extracellular acidification rates of human U937 and K562 leukemic cells treated with camptothecin or taxol. U937 cells treated with camptothecin or taxol for 30-60 min showed a continuous, irreversible decrease in extracellular acidification rate that was sensitive to amiloride. In contrast, U937 cells exposed to sodium azide showed an immediate, steep decrease in extracellular acidification rate that was reversible upon azide withdrawal. K562 cells required a >20-fold higher dose of camptothecin to promote similar changes in the extracellular acidification rate, with a corresponding resistance in their susceptibility to camptothecin- or taxol-induced apoptosis. The data show that irreversible commitment to apoptosis is associated with rapid metabolic changes that are reflected by decreased extracellular acidification rate and regulated by the Na+/H+ antiporter. Moreover, detection of extracellular acidification rate changes was not restricted to a particular cell type or apoptosis pathway, making this a potentially useful tool to screen compounds for pro-apoptotic activity.

Original languageEnglish (US)
Pages (from-to)23-30
Number of pages8
JournalEuropean Journal of Pharmacology
Volume465
Issue number1-2
DOIs
StatePublished - Mar 28 2003

Bibliographical note

Funding Information:
The authors wish to thank Josy Mayor and Betty Rosenbaum for technical help and Dr. Richard Metz and Dr. J. John Cohen for critical review of the manuscript. This work was supported in part by NIH grants CA83755 (to JFM) and GM46535 (to DSL).

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • Apoptosis
  • Extracellular acidification rate
  • Leukemic cell line
  • Microphysiometry
  • Na/H antiporter

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