title: Deprive to kill: glutamine closes the gate to anticancer monocarboxylic drugs.
abstract: 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.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Cardaci
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Ciriolo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D005973:Glutamine / Q000172:deficiency* / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D011773:Pyruvates / Q000494:pharmacology*; D027981:Symporters / Q000378:metabolism; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D000970:Antineoplastic Agents; D005973:Glutamine; D027501:Monocarboxylic Acid Transporters; D011773:Pyruvates; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C017092:bromopyruvate