Glutamine deprivation enhances antitumor activity of 3-bromopyruvate through the stabilization of monocarboxylate transporter-1
Cancer research, 2012•AACR
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 …
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 …
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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