Exciting News from the Hammock Lab
In research led by postdoctoral researcher Zuodong Zhang, a team of 16 scientists discovered a key mechanism by which dietary omega-3 fatty acids (fish oils) could reduce the tumor growth and spread of cancer, a disease that kills some 580,000 Americans a year.
The research is published today (April 3) in the Proceedings of the National Academy of Sciences (PNAS). They discovered cytochrome P450 epoxygenase metabolites of omega-3 fatty acid DHA or epoxy docosapentaenoic acids (EDPs) block blood supply to the tumor and thus inhibit tumor growth and metastasis.
The natural EDPs were further stabilized by a drug called a soluble epoxide hydrolase inhibitor which is already under development to control pain and hypertension.
“Many human studies have shown that omega-3 fatty acids reduce the risks of cancers, but the mechanism is poorly understood,” said Zhang, a postdoctoral researcher who focuses his research on lipid mediators on angiogenesis, tumor growth and metastasis. “Our study provides a novel mechanism by which these omega-3 lipids inhibit cancer.”
“We demonstrated that EDPs have very potent anti-cancer and anti-metastatic effects,” Zhang said. “Current anti-cancer drugs that block angiogenesis (the formation of new blood vessels to fuel tumor progression) can cause serious side effects such as hypertension. By blocking angiogenesis by a new mechanism and by widening blood vessels, EDPs could block tumor growth with reduced side effects in cancer patients.”
The studies, conducted on mice, also suggest that a combination of omega-3 diet and some anti-cancer drugs such as sorafenib, “could not only be efficacious to treat cancers but reduce potential side effects,” said Zhang, who received his doctorate in food science from the University of Wisconsin-Madison.
“Thus the effects of the soluble epoxide hydrolase inhibitors have opposite effects depending on whether the background lipid mediators are omega 3 or omega 6,” Hammock said. “Assuming that humans are mice (the study involved mice), the prediction is that with some cancer drugs--particularly the ones like sorafenib and regorafenib that are potent epoxide hydrolase inhibitors as well as anti-angiogenic agents--these could be more effective with a high omega 3 and low omega 6 background.”
“This is an exciting step towards our full appreciation of the impact of bioactive products from the DHA metabolome,” said Charles Serhan of Harvard Medical School, an expert on omega-3 autacoids and inflammation who is the Simon Gelman Professor of Anesthesia, Periopterative and Pain Medicine, Harvard Medical School. “This (UC Davis) contribution places metabolic conversion of omega-3 DHA to epoxy DHA products pivotal in vascular mechanisms key in cancer and vascular biology. It will be exciting to watch these important findings translated to humans for new evidence based treatments for angiogenesis, tumor growth and cancer metastasis.”
Said cardiologist Jonathan Lindner of the Oregon Health & Science University: “New drug strategies for fighting cancer could emerge from knowledge of how the body uses nutrition to promote health. Diet has been shown to influence susceptibility to many types of cancer, and also to influence rate of tumor progression and response to chemotherapy. This information has been leveraged to make reasonable recommendations on diet in patients with cancer. Perhaps more importantly, by uncovering how diet influences tumor development and growth, it may be possible to develop new drugs that work through the same beneficial pathways.”
“The study by Zhang and colleagues has uncovered a previously unrecognized anti-cancer effect of omega-3 fatty acids which are an important lipid component of diets that have been developed to prevent heart disease and cancer,” Lindner said. “The authors have demonstrated that metabolites of these lipids can act to suppress the growth of new blood vessels that are necessary to feed tumor growth. By shutting off the tumor’s blood supply, these compounds can act to dramatically slow tumor growth and prevent metastasis. The results from this suggest that new drug strategies for fighting cancer could emerge from knowledge of how the body uses nutrition to promote health.”
Read more about the research on the UC Davis Department of Entomology website and see photos of some of the co-authors.
UC Davis postdoctoral researcher Zuodong Zhang. (Photo by Kathy Keatley Garvey)