Controlling AGE'S Pharmacologically 

StAGEs of Cancer

Grape compound could reduce cancer-linked molecule in the diet

by Sver Aune

Could a common byproduct of the Western diet thought to promote cancer be reduced pharmacologically? Researchers at MUSC Hollings Cancer Center are testing compounds designed to block advanced glycation end products (AGEs) in patients with metastatic breast cancer who are receiving endocrine therapy. The pilot trial is led by Carolyn D. Britten, M.D., associate director for clinical investigations at Hollings, and inspired by the preclinical work of MUSC cancer biologist David P. Turner, Ph.D.

Scientists have known that patients with diabetes have high concentrations of AGEs in their blood. Yet Turner is among the first researchers to study how AGEs set the stage for cancer. AGEs accumulate in the body as a byproduct of breaking down sugar but are also found in red meats and fried and processed foods. Once in the body, they cause the formation of reactive oxygen species that can encourage the development and spread of cancer.

“AGEs are highly volatile and promote inflammatory and immune responses in the body,” says Turner. “We want to try to reduce AGEs in cancer patients because those responses may contribute to the return of cancer.”

Britten’s trial will test whether AGEs can be reduced pharmacologically with a compound isolated from grapes called oligomeric proanthocyanidin complex (OPC) in women with estrogen receptor–positive metastatic breast cancer. Patients must be receiving endocrine therapy to block the production of estrogen that is likely driving metastasis. Patients will take the oral hypoglycemic metformin along with OPC for 12 weeks. AGE concentration in the blood will be tracked before and after treatment to see if AGEs drop as a result of receiving OPC and metformin.

This follows preclinical studies by Turner that found that AGE levels were the highest in tumors of men with the worst prognosis for prostate cancer. A trial already underway in patients with prostate cancer, led by Michael B. Lilly, M.D., associate director of translational research at Hollings, is also tracking the reduction of AGEs in men taking OPC. In a recently completed trial, Turner worked with Marvella E. Ford, Ph.D., associate director of population sciences and cancer disparities, and Gayenell Magwood, Ph.D., professor in the College of Nursing and showed that exercise and a healthy diet can reduce AGE levels in breast cancer survivors. Turner was recently funded to conduct a dietary and physical intervention trial in prostate cancer survivors and to measure the effects of those interventions on AGE concentration.