DOI: 10.1097/01.COT.0000315974.95488.f9

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Issn Print: 0276-2234

Publication Date: 2008/03/25


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Preclinical & Mechanistic Studies

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The Ohio State University researchers are also continuing to do animal and in vitro studies to more carefully identify the mechanisms by which the berries inhibit disease carcinogenesis. In a chemically induced model of esophageal cancer, supplementation of the diet with freeze-dried berries reduced cancer by as much as 75%, when the berries made up 10% of the diet by weight.
Similarly, in a chemically induced model of colon cancer, the reduction was as much as 80%. In both models, there was a decline in molecular markers of cell proliferation and inflammation, including COX-2 and iNOS. There was also a decline in VEGF and a corresponding inhibition of angiogenesis.
“I will tell you that the inhibition of COX-2 expression and VEGF is about as good with berries as we have gotten with specific inhibitors of these two genes,” Gary Stoner, PhD, said during his presentation at the meeting. Using a microarray analysis, the scientists have found that berries induce widespread changes in gene expression. Microarrays from animals exposed to the chemical carcinogen, N-nitrosomethylbenzylamine (NMBA), which is used to induce esophageal cancer, showed a shift in expression of 2,261 genes compared with control animals.
When the animals were fed berries for two weeks prior to exposure, expression of 462 of the NMBA-affected genes was shifted again, with more than half returning to near normal expression patterns. Although Dr. Stoner did not discuss individual genes detected in the arrays, it was clear that supplementing the diet with black raspberries attenuated the carcinogen's impact significantly.
The extensive preclinical work has not gone unnoticed by other researchers in the cancer prevention field. “I remember talking to Gary [Stoner] 10 years ago, and I think he was talking about doing clinical trials then, but he was in the midst of doing animal and laboratory studies with his berries and studies,” said Jed W. Fahey, ScD, Faculty Research Associate at the Lewis B. and Dorothy Cullman Cancer Chemoprotection Center at Johns Hopkins. “Because he stayed with it and developed a lot of the science along the way, he's now able to move it to the clinic. If you get that far, you know that you've likely made a lot of progress.”
Dr. Stoner and collaborators at the university are working to identify specific components of black raspberries that have the dramatic anti-cancer effects. Fractionation experiments indicate that the anthocyanins, which give the berries their dark color, are important, but do not account for the entire effect. The team was surprised to find that some of the non-anthocyanin fractions also had an inhibitor impact in cell cultures.
The majority of the group's work has been with black raspberries, but they have also found that strawberries also inhibit cancer development in some animals models. Blueberries, by contrast, contain a substantially different profile of anthocyanins and do not appear to be protective in the same model systems, according to Dr. Stoner. Although the researchers use black raspberries grown specifically for them on the same farm year after year, grocery store berries do appear to have some of the same activity.
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