title: Glutamine deprivation enhances antitumor activity of 3-bromopyruvate through the stabilization of monocarboxylate transporter-1.
abstract: Anticancer drug efficacy might be leveraged by strategies to target certain biochemical adaptations of tumors. Here we show how depriving cancer cells of glutamine can enhance the anticancer properties of 3-bromopyruvate, a halogenated analog of pyruvic acid. Glutamine deprival potentiated 3-bromopyruvate chemotherapy by increasing the stability of the monocarboxylate transporter-1, an effect that sensitized cells to metabolic oxidative stress and autophagic cell death. We further elucidated mechanisms through which resistance to chemopotentiation by glutamine deprival could be circumvented. Overall, our findings offer a preclinical proof-of-concept for how to employ 3-bromopyruvate or other monocarboxylic-based drugs to sensitize tumors to chemotherapy.
authors: Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, Rome, Italy.
authors: Simone
authors: S
authors: Cardaci
authors: Salvatore
authors: S
authors: Rizza
authors: Giuseppe
authors: G
authors: Filomeni
authors: Roberta
authors: R
authors: Bernardini
authors: Fabio
authors: F
authors: Bertocchi
authors: Maurizio
authors: M
authors: Mattei
authors: Maurizio
authors: M
authors: Paci
authors: Giuseppe
authors: G
authors: Rotilio
authors: Maria Rosa
authors: MR
authors: Ciriolo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D042963:Electron Transport Complex II / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D018384:Oxidative Stress; D055550:Protein Stability / Q000187:drug effects; D059748:Proteolysis; D011773:Pyruvates / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D027501:Monocarboxylic Acid Transporters; D011773:Pyruvates; D005973:Glutamine; C017092:bromopyruvate; D042963:Electron Transport Complex II; D005974:Glutamate-Ammonia Ligase