~ 021109 Quercetin Shown to Help Protect Against Colon Cancer by Reducing Inflammation

In research published in the January, 2009 issue of the Journal of Nutrition, scientists at Texas A & M University report their finding of a mechanism for quercetin against the development of colon cancer. Quercetin is a molecule found in plant foods such as onions, apples and peppers which has previously shown a protective effect against the disease.

For their research, Texas AgriLife Research scientist Dr Nancy Turner and her colleagues gave 40 rats diets supplemented with or without quercetin. During the second and fourth weeks of the experiment, the animals were injected with azoxymethane, a carcinogen used to induce colon cancer in rodents, or with saline as a control. Four weeks following the last injection, the rats' colons were examined.

Animals that received quercetin had fewer high multiplicity aberrant crypt foci, a marker or predictor of tumor formation that had previously been shown to be reduced by quercetin. "Early lesions in a colon are some of the first true changes in the colon that can be observed visually," Dr Turner remarked. "This is not just something you see in our animal model. You see it in human patients as well."

Quercetin was also associated with a reduction in cell proliferation and an increase in apoptosis compared with that observed in animals that received unsupplemented diets. "We were able to decrease the number of cells that were proliferating in the colon," stated Dr Turner. "And we were able to increase the number of cells that were undergoing apoptosis. So the net effect of that is, we were able to maintain almost a normal number of cells."

The team found a reduction in proinflammatory enzymes known as COX-1 and COX-2 in rats that received quercetin. An increase in COX-1 has been observed prior to the elevation of -- COX-2 that occurs in colon cancer. The authors concluded that "It is possible the effects on proliferation and apoptosis resulted from the tendency for quercetin to suppress the expression of proinflammatory mediators."

"COX-2 is an inducible protein that is expressed in the body when there is some kind of external stimulus to a cell," Dr Turner explained. "We think of high levels of COX-2 as being a bad thing. We did see that both groups -- both the control groups and the carcinogen-injected groups that were consuming quercetin in their diets -- had lower levels of both COX-1 and COX-2. So that would tend to suggest that there may be opportunity for quercetin to suppress tumor development."

"The nice thing is that albeit high relative to what you see in the American diet, the level used in this study is actually similar to what can be achieved in diets around the world such as in, say, the Mediterranean-style diets," Dr Turner commented. "So it's not an unachievable goal for us good ol' Americans if we do the right thing with our food consumption."

Related Health Concern: Colorectal cancer

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the few agents known to prevent the development of colorectal cancer (Chan TA 2006). Aspirin or NSAID use results in an impressive reduction in the risk of developing colorectal cancer (Janne PA et al. 2000). In two randomized, placebo-controlled trials, aspirin decreased the risk of polyp recurrence, considered a precursor to cancer (Baron JA et al. 2003; Sandler RS et al. 2003); Moran EM 2002; Nakatsugi S et al 1997). Other trials have shown that NSAIDs such as sulindac (Clinoril®) and celecoxib (Celebrex®) decrease the frequency of colorectal adenomas in patients with familial adenomatous polyposis (Jalving M et al. 2005h).

NSAIDs inhibit cyclooxygenase (COX) enzymes and prostaglandin synthases, which is at least partly responsible for their anti-cancer effects.

A 9.4-year epidemiological study showed that COX-2 activation was related to more advanced tumor stage, tumor size, and lymph node metastasis, as well as diminished survival rates among colorectal cancer patients (Sheehan KM et al 1999). With regular use of aspirin (a nonspecific COX-2 inhibitor, but also an anticoagulant), the risk of dying from the disease decreased (Thun MJ et al 1991).

Thus, COX inhibitors have a pivotal role in the prevention and adjuvant treatment of colon cancer. However, the benefits observed with taking prescription COX-2 inhibitors such as Celebrex® (100-200 mg taken every 12 hours) for prolonged periods are accompanied by side effects (Tsujii M et al 1998). Therefore, nutritional supplements that naturally suppress COX-2 such as curcumin (3600 mg/day) could be considered (Gescher A 2004); others include bioflavonoids (250 to 1800 mg/day) and silymarin (420 mg/day) (Pares A et al 1998; Boari C et al 1981).

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