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Title: Intracellular ATP levels determine cell death fate of cancer cells exposed to both standard and redox chemotherapeutic agents
Authors: Verrax, Julien ×
Dejeans, Nicolas
Sid, Brice
Glorieux, Christophe
Calderon, Pedro Buc #
Issue Date: Dec-2011
Publisher: Elsevier
Series Title: Biochemical Pharmacology vol:82 issue:11 pages:1540-1548
Abstract: Cancer cells generally exhibit high levels of reactive oxygen species (ROS) that stimulate cell proliferation and promote genetic instability. Since this biochemical difference between normal and cancer cells represents a specific vulnerability that can be selectively targeted for cancer therapy, various ROS-generating agents are currently in clinical trials, either as single agents or in combination with standard therapy. However, little is known about the potential consequences of an increased oxidative stress for the efficacy of standard chemotherapeutic agents. In this context, we have assessed the influence of an oxidative stress generated by the combination of ascorbate and the redox-active quinone menadione on the capacity of melphalan, a common alkylating agent, to induce apoptosis in a chronic myelogenous leukemia cell line. Our data show that oxidative stress did not inhibit but rather promoted cancer cell killing by melphalan. Interestingly, we observed that, in the presence of oxidative stress, the type of cell death shifted from a caspase-3 dependent apoptosis to necrosis because of an ATP depletion which prevented caspase activation. Taken together, these data suggest that ROS-generating agents could be useful in combination with standard chemotherapy, even if all the molecular consequences of such an addition remain to be determined.
URI: 
ISSN: 0006-2952
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Cell Death Research & Therapy
× corresponding author
# (joint) last author

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