Glucose metabolism could be used to selectively destroy cancer cells

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.

"If tumor cells have defects in their mitochondrial respiratory mechanism it would imply that cancer cells have a potentially lethal metabolic defect that is compensated for by consuming more glucose," said Spitz, who also is co-director of the Free Radical Research Core in the Holden Comprehensive Cancer Center at the UI. "However, when a cancer cell has insufficient glucose metabolism to overcome this problem, the tumor cell's own mitochondrial metabolism could become lethal resulting in preferential cancer cell death."

Spitz added, "If the hypothesis is verified, this study will provide a very clear biochemical rationale for developing cancer therapies that both inhibit glucose metabolism and enhance free radical damage in tumor cells. Furthermore, such therapies could be highly effective for all types of cancer cells carrying similar defects in mitochondrial metabolism."

The Holden Comprehensive Cancer Center is Iowa's only National Cancer Institute (NCI)-designated comprehensive cancer center. NCI-designated comprehensive cancer centers are recognized as the leaders in developing new approaches to cancer prevention and cancer care, conducting leading edge research and educating the public about cancer. Visit the center online at http://www.uihealthcare.com/depts/cancercenter/.

University of Iowa Health Care describes the partnership between the UI Roy J. and Lucille A. Carver College of Medicine and UI Hospitals and Clinics and the patient care, medical education and research programs and services they provide. Visit UI Health Care online at http://www.uihealthcare.com.