Curcumin Shows Potential to Prevent Inflammation-Associated Colorectal Cancer, Restore Microbial Gut Ecology

Researchers at the UA Steele Children’s Research Center discover that curcumin may be a viable means to prevent inflammation-associated colorectal cancer, while also regulating the microbiota of the gut.

Researchers at the University of Arizona Steele Children’s Research Center have made another promising discovery about curcumin—the bioactive ingredient in turmeric—as a potentially viable means to prevent inflammation-associated colorectal cancer and balance the microbiota of the gut.

Dorrance Fellow, Rita-Marie McFadden, PhD“The microbiota of the gut is becoming recognized as a major player in health and disease,” said Fayez K. Ghishan, MD, professor and head, UA Department of Pediatrics and director of the UA Steele Center. “This is the first study to implicate the role of curcumin in modulating the microbiota of the gut and preventing colon cancer.”

Colorectal cancer—cancers of the colon and rectum—is the third-highest cause of cancer-related mortality in the United States. Individuals with Inflammatory Bowel Disease (Crohn’s disease and ulcerative colitis) have a higher chance of developing colon cancer.

The American Cancer Society estimates that in 2015, approximately 93,000 people in the United States will be diagnosed with colon cancer, 40,000 with rectal cancer and 50,000 will die from the disease.

Genetic components, environmental factors, inflammation and gut microbiota have been implicated as causing colorectal cancer and its progression. Diet, dietary supplements, exercise, control of body weight and nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed as the primary means to prevent colorectal cancer.

Curcumin has been to shown in a number of studies to have anti-cancer effects and to enhance the effects of chemotherapy or radiotherapy.

Pawel Kiela, PhD; Fayez K. Ghishan, MDDr. Ghishan, Pawel Kiela, PhD, associate professor, and their research team at the UA Steele Center have investigated the anti-inflammatory and anticancer properties of curcumin for several years.

In their latest study, Dorrance Fellow and then-PhD candidate Rita-Marie McFadden studied the effects of dietary supplementation with curcumin on the development of colorectal cancer and on the changes in the composition of gut microbiota in mice with inflammation-associated colorectal cancer.

Under the guidance of Drs. Kiela and Ghishan, McFadden worked with a team of researchers at the UA Steele Center and Northern Arizona University. She was first author on their study, “The Role of Curcumin in Modulating Colonic Microbiota During Colitis and Colon Cancer Prevention,” published in Inflammatory Bowel Diseases in July.

“Our research showed that specific doses of curcumin greatly reduced or prevented tumors from forming in mice with colitis-associated colon cancer,” said McFadden. “Moreover, this was associated with an increase in the diversity of bacteria within the colon, demonstrating how diet and microbial populations can play a significant role in disease prevention and treatment, especially during the switch from chronic inflammation to the onset of cancer. This is especially promising for patients with chronic inflammatory bowel disease who are at a high risk for developing colon cancer.”

In the research model, the investigators used genetically modified mice, which lack an anti-inflammatory protein interleukin 10 (IL-10), and thus spontaneously develop intestinal inflammation. They then were treated with azoxymethane (AOM), a chemical carcinogen capable of selectively inducing the formation of colon cancer.

The study showed that suppression of the mucosal inflammation was not necessary to see the chemopreventive effects of curcumin. In fact, at a dose of 0.5 percent in the diet, curcumin treatment led to a complete prevention of tumor formation. Moreover, in healthy and IL-10-deficient mice, long-term curcumin supplementation helped maintain bacterial richness and microbial diversity, the hallmark of healthy gut. This was associated with the expansion of Lactobacillales (represented mainly by genus Lactobacillus, which also includes known probiotic strains of bacteria). The relative abundance of the Lactobacillales order was decreased in mice with intestinal inflammation and cancer, and dietary curcumin restored this order to control levels.

This finding may be highly relevant for the protective effects of curcumin, as Lactobacillus strains have been used successfully in preventing colorectal cancer in animal models and have been shown to protect against DNA damage, and Lactobacillus genus has been associated with stopping cell division and inducing apoptosis (a form of cell death) in colon cancer cell lines.

“Curcumin is a safe supplement and may have significant clinical value both in the general population and in those with inflammatory bowel disease in which increased occurrence of colorectal cancer has been documented,” said Dr. Kiela.

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Funding for this research was provided by the National Institutes of Health (NIH) Grant R01DK67286 and by the Dorrance Foundation fellowship.