Deprive to kill: glutamine closes the gate to anticancer monocarboxylic drugs

S Cardaci, MR Ciriolo - Autophagy, 2012 - Taylor & Francis
S Cardaci, MR Ciriolo
Autophagy, 2012Taylor & Francis
Killing properties of antitumor drugs can be enhanced by strategies targeting biochemical
adaptations of cancer cells. Recently, we reported that depriving cancer cells of glutamine is
a feasible approach to enhance antitumor effects of the alkylating analog of pyruvic acid, 3-
bromopyruvate, which rely on the induction of autophagic cell death by metabolic-oxidative
stress. 3-bromopyruvate chemopotentiation is the result of its increased intracellular uptake
mediated by the monocarboxylate transporter 1, whose expression is post-transcriptionally …
Killing properties of antitumor drugs can be enhanced by strategies targeting biochemical adaptations of cancer cells. Recently, we reported that depriving cancer cells of glutamine is a feasible approach to enhance antitumor effects of the alkylating analog of pyruvic acid, 3-bromopyruvate, which rely on the induction of autophagic cell death by metabolic-oxidative stress. 3-bromopyruvate chemopotentiation is the result of its increased intracellular uptake mediated by the monocarboxylate transporter 1, whose expression is post-transcriptionally increased upon glutamine withdrawal. Overall, our results identified the metabolic condition able to increase the selectivity of 3-bromopyruvate targets in neoplastic tissues, thereby providing a stage for its use in clinical settings for targeting malignancies and represent a proof of principle that modulation of glutamine availability can influence the delivery of monocarboxylic drugs into tumors.
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