A second study conducted by researchers from the James Cancer Hospital and Ohio State University will evaluate whether strawberries can prevent or retard the development of oral cancers. Although prevalence of oral cancer is relatively low in the United States (2.5 percent of all cancers), there are high-risk areas in the Appalachian regions where rates are much higher. Like esophageal cancer, the prognosis for sufferers is not favorable: only half survive more than five years after diagnosis. In addition, current treatments are relatively ineffective and potentially harmful. Thus, identifying preventive measures could greatly benefit segments of the population at elevated risk, such as former smokers.

This study will use an animal model of oral carcinogenesis, the hamster cheek pouch (HCP), which has been shown to be an excellent model because the cell and tissue changes that occur during early cancer are similar between hamsters and humans. Two different protocols will be used. In the first, the hamsters will be given lyophilized strawberries in the diet beginning one week before induction of oral cancer and continuously for 13 weeks thereafter. This will reveal whether strawberries can prevent the formation of cancer.

In the second protocol, the animals’ HCPs will first be exposed to a chemical carcinogen for six weeks and then treated topically with a lyophilized strawberry solution. This will reveal whether strawberries can intervene in the cancer process in cells that have already been initiated. If successful, the study will pave the way for a clinical trial in humans.

Weghorst et al, James Cancer Hospital, Ohio State University

A clinical study sponsored by the California Strawberry Commission (CSC) will evaluate whether strawberries can inhibit the development of cancer of the esophagus. The study will be carried out in China, which has one of the highest rates of this cancer in the world. The age-standardized incidence of esophageal cancer in China is 27.4 per 100,000 population, compared to an average rate of 13.8 in less developed regions and 6.8 in more developed regions worldwide.*

Overall, esophageal cancer is the 7th most common type of cancer in the world, but it is the second most deadly. It has a survival rate of 14 percent, second only to pancreatic cancer at 4 percent (lung cancer has the third lowest survival rate at 15 percent). Because of the lack of effective treatment and poor prognosis for its victims, esophageal cancer is a prime candidate for chemoprevention.

The exact causes are still unknown, but risk factors include vitamin and mineral inadequacies, excessive tobacco use, combined alcohol and tobacco use, viral infections or contaminants in foods and water, and high intakes of hot and spicy foods. One leading hypothesis is that esophageal cancer is triggered by chemical carcinogens called nitrosamines, which are found in smoked and pickled foods. Several of these compounds, notably N-nitrosodemethylamine (NDMA), N-nitrosodiethylamine (NDEA) and N-(1- methylacetonyl-N-3-methybutyl) (NMBA) have been shown to produce esophageal lesions in laboratory animals. These compounds have also been identified in pickled vegetables and other foods that are eaten in high amounts in the regions most affected by esophageal cancer.

Ninety to 95 percent of esophageal cancers are of a type called squamous cell carcinoma. The actual progression to cancer is preceded by a non- cancerous stage called dysplasia. Thus, people with dysplasia are at high risk, but may potentially be spared progression to cancer if preventive strategies are successful.

Studies conducted by researchers at the College of Medicine and Public Health at Ohio State University previously showed that freeze-dried black raspberry extract inhibited esophageal tumors induced by nitrosamines by up to 65 percent. Four biochemical markers of the cancer initiation process were identified and measured. These studies provided a biochemical rationale for attempting chemoprevention in humans using strawberry extracts, which contain protective compounds similar to those found in black raspberries.

In the new trial, subjects with mild to severe dysplasia will be given either 50 or 100 grams of freeze-dried strawberries mixed in a breakfast drink daily for six months. Subsequent biopsies will measure markers of anti-proliferation of cancer cells, anti-inflammatory effects, and the effects of strawberries on gene transcription.

Ohio State expects the trial to be completed over the course of the next three years.

*Data source: International Agency for Research on Cancer (IARC), a division of the World Health Organization. www-dep.iarc.fr/

Stoner et al, James Cancer Hospital, Ohio State University

Researchers at the University of Athens tested the ability of ellagic acid to bind to estrogen receptor subtypes ER alpha (involved with reproductive organ function) and ER beta (involved with regulation of bone metabolism). At low concentrations, ellagic acid had a small but significant estrogenic activity via the alpha receptors, but it was a complete estrogen antagonist via the beta receptors. Further evaluation showed that ellagic acid was a potent antiestrogen in breast cancer-derived cells in vitro. The findings suggest that ellagic acid may be a natural selective estrogen receptor modulator (SERM).

Papoutsi Z, et. al. Evaluation of estrogenic/anti- estrogenic activity of ellagic acid via the estrogen receptor subtypes ER alpha and ER beta. J Agric Food Chem. 2005, 53:7715-20.

Marie Olsson, a researcher at the Swedish University of Agricultural Sciences, presented a study at a recent FAV Health 2005 International Symposium on Human Health Effects of Fruits and Vegetables, that identified a potential role for strawberries in cancer prevention. Olsson found a direct, concentration- dependent inhibition of the proliferation of in vitro breast and colon cancer cells after introduction of a strawberry extract. The researchers concluded that a synergistic effect of phytonutrients in strawberries (i.e., ellagic acid, anthocyanins, hydrocinnamic acids) was most likely responsible for strawberries’ effect.