Treating Metabolic Syndrome is Studied to Reduce Pancreatic Cancer Risk

Division of Cancer Biology

Two decades ago, the term “metabolic syndrome” was adopted by researchers and clinicians to describe the cluster of disease risk factors, including resistance to insulin, that develop as people accumulate excess weight. “Knowing these specific processes and targets in the body, we can begin to develop and evaluate ways to prevent and treat metabolic syndrome” as a way to reduce the risk of certain cancers (such as breast and prostate), as well as type 2 diabetes and cardiovascular disease, noted Jin-Rong Zhou, Ph.D., director of the Nutrition/Metabolism Laboratory at Beth Israel Deaconess Medical Center in Boston and assistant professor of surgery at Harvard Medical School.

In 2007, Dr. Zhou was the co-director of a Harvard symposium on “Metabolic Syndrome and the Onset of Cancer,” where Dr. Zhou described NCI-supported work in his lab showing that a combination of dietary soy and green tea dramatically reduced four of the risk factors for metabolic syndrome in mice.

So far, Dr. Zhou and others have provided evidence for this link only in breast and prostate cancer. He is now trying to determine whether the syndrome also increases the risk of pancreatic cancer. “We don’t really know what causes pancreatic cancer and have not been able to develop effective treatments,” he said. Pancreatic cancer is now the fourth leading cause of cancer death, which is why Dr. Zhou believes that finding preventive approaches is crucial.

“We are seeing increases in both metabolic syndrome and pancreatic cancer in the population,” Dr. Zhou explained. “If one is causing the other, and we can treat the development of metabolic syndrome, it could prevent a lot of disease that we really don’t know how to otherwise effectively treat.”

With funding from NCI*, Zhou’s lab is exploring whether green and black tea can prevent metabolic syndrome in mice that are genetically-engineered to develop pancreatic cancer. By feeding the mice a diet high in fat and white sugars, the researchers can track elements of the metabolic syndrome to see which may be contributing directly to the appearance and growth of the cancer. “The pancreas is the major organ producing insulin,” Dr. Zhou noted. “We think that one of the core risk factors for metabolic syndrome – insulin resistance – could be a factor in pancreatic cancer development.”

In his earlier work using a mouse model with prostate cancer, Zhou found that mice given compounds extracted from both teas had significantly lowered body weight when compared to mice not given the tea extracts, although the groups consumed the same number of calories. Other biomarkers for metabolic syndrome were also reduced. The new study in pancreatic cancer mice will allow the researchers to evaluate how the diet might impact some of the other risk factors that comprise metabolic syndrome, including hypertension, low HDL cholesterol, and high triglycerides in the blood. Dr. Zhou’s research team will try to correlate changes in these risk factors with the development of pre-cancerous, pancreatic lesions in the mice.

Many people drink green and black tea with minimum side effects, Dr. Zhou commented. Positive results from the mouse studies could lead directly to clinical trials in people, testing a preventive strategy for pancreatic cancer that is practical and safe.

NCI Program Director Ming Lei, Ph.D., commented, “Dr. Zhou’s pilot study represents an increasingly important component of DCB’s cancer cell metabolism portfolio. Using well-controlled animal models, the research will provide high-quality experimental evidence that is critical for assessing the role of metabolic disorders in pancreatic cancer development, and the efficiency of natural products such as green tea as cancer prevention remedies.”