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Tuesday, April 7, 2015. The February 2015 issue of Cancer Prevention Research published the finding of researchers from China's Lanzhou University and Case Comprehensive Cancer Center in Ohio of an additive benefit for vitamin D and the antidiabetic drug metformin in the prevention of colorectal cancer in rodent models of the disease.
Vitamin D helps regulate cell proliferation, differentiation and apoptosis, while inhibiting the activation of a pathway (Wnt/β-catenin) that triggers genes responsible for colon cancer cell proliferation. In addition to suppressing the proliferation of colon epithelial cells and aberrant crypt foci (a precursor of colorectal polyps), metformin stimulates the AMP-activated protein kinase (AMPK) pathway, which reduces signaling and protein synthesis necessary for cancer cell growth.
Li Li, MD, PhD, of Case Western Reserve and colleagues administered varying doses of vitamin D3, metformin, both compounds, or an anti-inflammatory control drug for 18 weeks to rats given a compound that renders the colon susceptible to the development of neoplasia (precancerous cells). In another experiment involving mice that received a substance that causes colitis (which can lead to neoplasia), the animals were given the same treatments for 20 weeks.
In comparison with vitamin D or metformin alone, the combination of a moderate dose of vitamin D and metformin resulted in the formation of fewer aberrant crypt foci and tumors in both experiments. "Few colon neoplasias developed in the animals receiving moderate doses of metformin-vitamin D combination," reported Dr Li, who is the Case Comprehensive Cancer Center's associate director for prevention research. "On average, there was also a 40 percent decrease in the development of polyps in all animals receiving both drugs in combination compared to the control groups."
"In the two animal models, we showed that metformin and vitamin D3 did indeed work together," he observed. "Clearly, if we put the two together, they are much more potent in preventing colon neoplasia than by taking just either one of them alone. The medium dose also tells us that it is not necessary to take huge doses of the drugs to have a cancer-prevention effect. If the results in the animal models translate to humans, that will be a highly significant finding in colorectal cancer prevention."
"Persons with a 10 millimeter or larger adenoma polyp or high-grade neoplasia have a 50 percent chance for recurrence within four years," Dr Li noted. "We can screen them for colon cancer with colonoscopy every few years, but we don't have much to offer them in terms of prevention. This metformin-vitamin D3 combo may provide an opportunity to prevent recurrence."
"There is a lot of talk now about drug repurposing today where one drug developed for one condition can be used for an entirely different one," he added. "Here we have two well-proven medicines that if you put them together, they appear to prevent cancer, and they are safe."
"Millions of individuals with diabetes, even those who are pregnant, are taking metformin, and individuals with vitamin D deficiency are taking vitamin D3 medications," commented Case Comprehensive Cancer Center director Stanton Gerson, MD. "So metformin and vitamin D3 may already be providing a colorectal cancer prevention benefit to a significant number of people." |
