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

doi:10.1016/S0014-2999(03)01425-0

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

Veterinary Clinical Sciences

Research output: Contribution to journal › Article › peer-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 language	English (US)
Pages (from-to)	23-30
Number of pages	8
Journal	European Journal of Pharmacology
Volume	465
Issue number	1-2
DOIs	https://doi.org/10.1016/S0014-2999(03)01425-0
State	Published - 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).

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/S0014-2999(03)01425-0

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title = "Early changes in metabolism of leukemic cell lines upon induction of apoptosis by cytotoxic drugs",

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.",

keywords = "Apoptosis, Extracellular acidification rate, Leukemic cell line, Microphysiometry, Na/H antiporter",

author = "Sangeeta Khare and Yona Banai and Kuppan Gokulan and Roger Smith and Linthicum, {Darwin S.} and Modiano, {Jaime F.}",

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).",

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T1 - Early changes in metabolism of leukemic cell lines upon induction of apoptosis by cytotoxic drugs

AU - Khare, Sangeeta

AU - Banai, Yona

AU - Gokulan, Kuppan

AU - Smith, Roger

AU - Linthicum, Darwin S.

AU - Modiano, Jaime F.

N1 - 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).

PY - 2003/3/28

Y1 - 2003/3/28

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Extracellular acidification rate

KW - Leukemic cell line

KW - Microphysiometry

KW - Na/H antiporter

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

Abstract

Bibliographical note

Keywords

UN SDGs

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