Deprive to kill

摘要

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.