Abstract
Apoptosis, induced in tumors by anticancer agents, is characterized by caspase activation, impaired cellular respiration and decreased cellular ATP. Respiration in Jurkat and HL-60 cells treated with doxorubicin, dactinomycin or platinum drugs is measured using a Pd(II) phosphor that monitors [O2] in cell suspensions as a function of time. Cellular ATP is determined using the luciferin-luciferase bioluminescence system. Intracellular caspase activation is measured by allowing caspases to cleave Ac-DEVD-AFC to the fluorescent AFC, which is detected on HPLC. Comparing the ways in which respiration, ATP level, and caspase activity vary with time points up differences between the mechanisms of actions of doxorubicin, dactinomycin and the platinum compounds. These methods accurately determine the sensitivity of tumors to anticancer drugs.
Keywords: Apoptosis, cellular ATP, 7-amino-4-trifluoromethyl coumarin, pan-caspase inhibitor, doxorubicin
Current Drug Therapy
Title: Study on Caspase-Induced Mitochondrial Dysfunction by Anticancer Drugs
Volume: 2 Issue: 3
Author(s): Zhimin Tao, Matthew P. Morrow, Harvey S. Penefsky, Jerry Goodisman and Abdul-Kader Souid
Affiliation:
Keywords: Apoptosis, cellular ATP, 7-amino-4-trifluoromethyl coumarin, pan-caspase inhibitor, doxorubicin
Abstract: Apoptosis, induced in tumors by anticancer agents, is characterized by caspase activation, impaired cellular respiration and decreased cellular ATP. Respiration in Jurkat and HL-60 cells treated with doxorubicin, dactinomycin or platinum drugs is measured using a Pd(II) phosphor that monitors [O2] in cell suspensions as a function of time. Cellular ATP is determined using the luciferin-luciferase bioluminescence system. Intracellular caspase activation is measured by allowing caspases to cleave Ac-DEVD-AFC to the fluorescent AFC, which is detected on HPLC. Comparing the ways in which respiration, ATP level, and caspase activity vary with time points up differences between the mechanisms of actions of doxorubicin, dactinomycin and the platinum compounds. These methods accurately determine the sensitivity of tumors to anticancer drugs.
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Cite this article as:
Tao Zhimin, Morrow P. Matthew, Penefsky S. Harvey, Goodisman Jerry and Souid Abdul-Kader, Study on Caspase-Induced Mitochondrial Dysfunction by Anticancer Drugs, Current Drug Therapy 2007; 2 (3) . https://dx.doi.org/10.2174/157488507781695621
DOI https://dx.doi.org/10.2174/157488507781695621 |
Print ISSN 1574-8855 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3903 |
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