BOSTON, Aug. 18, 2015 -- Cranberries are often touted as a way to protect against urinary tract infections, but that may be just the beginning. Researchers fed cranberry extracts to mice with colon cancer and found that the tumors diminished in size and number. Identifying the therapeutic molecules in the tart fruit could lead to a better understanding of its anti-cancer potential, they say.
The team will describe their approach in one of more than 9,000 presentations at the 250th National Meeting & Exposition of the American Chemical Society (ACS), the world's largest scientific society, taking place here through Thursday.
According to the American Cancer Society, one in 20 Americans will develop colon cancer at some point in his or her lifetime. While progress has been made on the detection and treatment of colon cancer, it remains the second leading cause of cancer-related deaths in the U.S.
Colon cancer may offer a particularly good target for a dietary treatment, says Catherine Neto, Ph.D., simply due to the anatomy of digestion. "Cranberry extracts may also afford protection toward other cancers, but it seems reasonable to look at colon cancer," she says. "Cranberry constituents and metabolites should be bioavailable to the colon as digestion proceeds."
In previous studies, Neto and colleagues at the University of Massachusetts, Dartmouth, found that chemicals derived from cranberry extracts could selectively kill off colon tumor cells in laboratory dishes. "We've identified several compounds in cranberry extracts over the years that seemed promising, but we've always wanted to look at what happens with the compounds in an animal model of cancer," Neto says. This led to a collaboration with Hang Xiao, Ph.D., of the University of Massachusetts, Amherst. His team had developed a mouse model that mimics the type of colon cancer associated with colitis, an inflammatory bowel condition that affects hundreds of thousands of people in the U.S.
For Neto's part, her team generated three powdered cranberry extracts: a whole fruit powder, an extract containing only the cranberry polyphenols, and one containing only the non-polyphenol components of the fruit. Some evidence suggests that polyphenols have anti-inflammatory properties, and she wanted to assess their contribution to the cranberry's overall impact.
The researchers mixed the cranberry extracts into the meals of mice with colon cancer. She notes that the mice do not seem to mind the tart flavor. After 20 weeks, the mice given the whole cranberry extract had about half the number of tumors as mice that received no cranberry in their chow. The remaining tumors in the cranberry-fed mice were also smaller. Plus, the cranberry extracts seemed to reduce the levels of inflammation markers in the mice.
"Basically, what we found was pretty encouraging. All preparations were effective to some degree, but the whole cranberry extract was the most effective," says Neto. "There may be some synergy between polyphenol and non-polyphenol constituents." Neto's graduate student Sarah Frade will present the work at the ACS meeting.
In the study, the researchers were careful not to give the mice an absurd amount of cranberry. "This is approximately equivalent to a cup a day of cranberries if you were a human instead of a mouse," Neto says. However, she's not sure someone could get the same benefits from juice, which lacks some of the components in the skin of the cranberry.
Currently, Neto is looking deeper into the cranberry to see if she can isolate individual components responsible for its anti-cancer properties. The researchers are also analyzing the metabolites in the mice that consumed the fruit extracts to better understand what happens due to mouse metabolism after the cranberry components are digested.
Neto acknowledges funding from the UMass President's Science and Technology Initiative.
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Inhibition of colon cancer growth and inflammation in cellular and mouse models by cranberry extracts (Vaccinium macrocarpon)
The ability of cranberry fruit extracts to inhibit colon carcinogenesis is under investigation using a combination of in vitro and in vivo approaches. Extracts and compounds from cranberry fruit (Vaccinium macrocarpon) were observed to decrease the proliferation of HCT116 and HT-29 colon tumor cells, while growth of CCD-18 normal colon cells was impacted to a lesser extent. A cranberry feeding study was conducted using AOM/DSS mice, a model of colitis-associated colon carcinogenesis. Mice were treated with azoxymethane and dextran sodium sulfate to induce inflammation-driven colon carcinogenesis, while receiving AIN-93 diet containing whole cranberry powder (WCP), a polyphenol-rich polar extract, a lipid-rich nonpolar extract, or no cranberry. After 20 weeks on WCP diet, the number of tumors and tumor volume per mouse were significantly decreased, by more than 50% compared to control, accompanied by a reduction in tissue markers of inflammation IL-1 and IL-6. Significant reductions in tumors and inflammation were also observed with the polar and nonpolar extracts. The identities of cranberry constituents and metabolites responsible is under investigation. The effects of the cranberry extracts and some of their major constituents, including proanthocyanidins and ursolic acid, on expression of IL-6 were determined in the colon cell lines using ELISA. Metabolic profiling using HPLC-DAD and LC-MS is also underway to determine changes in the composition of mouse colonic metabolites resulting from cranberry diets. These studies demonstrate potential for dietary cranberry to inhibit colon carcinogenesis through decreased inflammation.