Scientists have known for decades that cancer cells consume more glucose than normal cells. A longstanding assumption that the excess glucose metabolism was needed to make energy has not been borne out by research studies. This lack of understanding of why cancer cells need increased glucose metabolism has hampered the exploitation of this difference for cancer therapy.
University of Iowa Roy J. and Lucille A. Carver College of Medicine researchers in the Holden Comprehensive Cancer Center have been awarded a five-year, $1.5 million grant from the National Cancer Institute to investigate a novel hypothesis by which increased glucose metabolism could be used to selectively destroy cancer cells.
A research team, led by Douglas Spitz, Ph.D., UI associate professor of radiation oncology in the Free Radical and Radiation Biology Graduate Program, will test the hypothesis that cancer cells use more glucose than normal cells in order to overcome a potentially lethal cellular defect that causes cancer cells to produce excess oxygen free radicals.
Studies have suggested that a cellular organelle known as the mitochondrion may be the site of excess free radical production in cancer cells. Spitz's team will investigate whether cancer cells harbor defects in mitochondrial electron transport chain proteins that cause increased production of oxygen free radicals and reactive oxygen species derived from free radicals.
Spitz and his colleagues have discovered that glucose-deprived tumor cells die from oxidative stress. This stress is caused by an imbalance between harmful reactive oxygen species and protective anti-oxidants such as enzymes that neutralize reactive oxygen species. Glucose provides a major source of electrons for a group of antioxidant enzymes that breakdown reactive oxygen species, such as hydroperoxides. This could explain why cancer cells need extra glucose to boost their ability to remove these toxic substances.