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Supplementary Figure 1 from Glutamine Deprivation Enhances Antitumor Activity of 3-Bromopyruvate through the Stabilization of Monocarboxylate Transporter-1

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posted on 2023-03-30, 21:22 authored by Simone Cardaci, Salvatore Rizza, Giuseppe Filomeni, Roberta Bernardini, Fabio Bertocchi, Maurizio Mattei, Maurizio Paci, Giuseppe Rotilio, Maria Rosa Ciriolo

PDF file - 127K, Chemo-potentiation of 3-BrPA cytotoxicity is not associated with the activation of apoptosis

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ARTICLE 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. Cancer Res; 72(17); 4526–36. ©2012 AACR.

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    Cancer Research

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    ChemotherapyCombination chemotherapyDrug MechanismsCellular responses to anticancer drugsDrug-mediated stimulation of cell death pathwaysDrug ResistanceReversal of drug resistanceDrug TargetsPreclinical ModelsXenograft modelsSmall Molecule AgentsAlkylating agents

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