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Glucose linked to breast cancer cell death

Breast cancer cell death during radiation treatment can be enhanced by targeting glucose, UC Irvine endocrinology professor Dr. Ellis Levin reported in the journal Molecular Endocrinology.

Molecular Endocriinology journal, December 2012

In the cover article of the journal's December 2012 issue, Levin and his team wrote that lowering levels of this simple sugar molecule causes metabolic changes in breast cancer cells that can boost the toxic effects of radiation therapy.

This finding may have particular application in adjuvant therapies for estrogen receptor-positive breast cancer, said Levin, chair of the Division of Endocrinology in the UC Irvine School of Medicine’s Department of Medicine.

The team’s research shows that breast cancer cells respond to changes in glucose by shifting their metabolism from glycolysis to oxidative phosphorylation and the Krebs cycle, Levin said.

This is promoted by estrogen signaling through AMP kinase to activate the key enzyme, pyruvate dehydrogenase. This enzyme uses the glucose metabolite pyruvate for entry into mitochondrial pathways rather than glycolytic pathways.

By blocking pyruvate dehydrogenase activity in a lower glucose setting, radiation cytotoxicity—cell death—is markedly enhanced, undercutting estrogen as a survival factor in this type of malignancy.

“We propose that lowering glucose substrate and inhibiting PDH may augment adjuvant therapies for estrogen receptor-positive breast cancer,” the study concluded.

View the Molecular Endocrinology journal abstract >