Glutamine deprivation enhances antitumor activity of 3-bromopyruvate through the stabilization of monocarboxylate transporter-1

Simone Cardaci, Salvatore Rizza, Giuseppe Filomeni, Roberta Bernardini, Fabio Bertocchi, Maurizio Mattei, Maurizio Paci, Giuseppe Rotilio, Maria Rosa Ciriolo

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)4526-4536
Number of pages11
JournalCancer Research
Volume72
Issue number17
DOIs
Publication statusPublished - Sep 1 2012

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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