Discovery of colon cancer pathway could lead to new targeted treatments

11/03/2019

A new study, conducted by food science researchers at the University of Massachusetts have found a set of enzymes involved in tumour growth that could be targeted to prevent or treat colon cancer.
Speaking about it, study author Guosong Zhang said, “Our research identifies a novel therapeutic target and could help to develop novel strategies to reduce the risks of colon cancer." The study was published in the journal Cancer Research.
In their study, UMass Amherst researchers tested their hypothesis that once present, colon cancer was increased by enzymes known as cytochrome P450 (CYP) monooxygenases and the fatty acid metabolites they form, epoxyoctadecenoic acids (EpOMEs).
Researchers compared healthy mice and mice with colon cancer by performing metabolomics, a comprehensive and complex analysis of metabolites, which are produced when food and chemicals are broken down.
The researchers found that certain fatty acid metabolites were more abundant in colon cancer. "If a mouse has colon cancer, the plasma and colon concentrations of EpOMEs are very dramatically increased and the EpOME-producing enzymes, CYP monooxygenases, are overexpressed in the colon," Zhang said.
Researchers also studied human colon cancer cells, comparing them to normal colon cells, and found the same results: an overexpression, or plethora, of the CYP monooxygenase enzymes.
The experts then, using pharmacological and genetic approaches, removed or inhibited the CYP monooxygenase enzymes in mice with colon cancer and found that tumour growth was suppressed. "If you block the enzyme, colon cancer can be significantly reduced," Zhang added.
In an effort to determine which metabolites were involved in the colon cancer-enhancing effects, researchers studied the biological actions of CYP monooxygenase metabolites. In an in vitro test, they found that EpOME, but not other CYP monooxygenase metabolites, increased inflammation in both inflammatory and colon cancer cells. They then treated cancer-induced mice with EpOME and found an increase in the number and size of tumours. The researchers found that at a low dose, the metabolite can make colon cancer more aggressive," Zhang says.
Taken together, the results of the research demonstrate "that the previously unappreciated CYP monooxygenase pathway" could be explored for preventing or treating colon cancer, Zhang concluded. He further pointed out that previous studies have shown that some FDA-approved drugs inhibit CYP monooxygenases, including Micardis, a blood pressure medication, and Lopid, which is used to lower cholesterol. "That suggests that these drugs could be repurposed for preventing or treating colon cancer," Zhang said, adding, "And novel monooxygenase inhibitors could be developed for use in humans.”

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