Bruce D. Hammock, Ph.D.
University of California, Davis
NIEHS Grants R01ES02710, P42ES04699
NIEHS grantees report a key mechanism by which dietary omega-3 fatty acids could reduce the tumor growth and spread of cancer. The studies suggest that combining dietary omega-3 with some anti-cancer drugs could effectively treat cancers while reducing potential side effects.
Cell and mouse experiments showed that epoxy docosapentaenoic acids (EDPs), which are metabolites of the omega-3 fatty acid docosahexaenoic acid (DHA), inhibit tumor growth and metastasis by blocking the formation of new blood vessels. Administering a low-dose epoxide hydrolase inhibitor along with EDPs stabilized the EDPs in circulating blood, leading to approximately 70 percent inhibition of primary tumor growth and metastasis. The anti-cancer drugs sorafenib and regorafenib are FDA-approved kinase inhibitors that also inhibit epoxide hydrolase, and the researchers say that EDPs could provide a new way to block blood vessel growth while reducing side effects in cancer patients.
The researchers also found that a metabolite of the arachidonic acid (ARA) omega-6 fatty acid had the opposite effect of EDP, slightly increasing blood vessel growth and tumor progression in mice. This increase in blood vessel growth encourages wound healing and tissue repair.
Citation: Zhang G, Panigrahy D, Mahakian LM, Yang J, Liu JY, Stephen Lee KS, Wettersten HI, Ulu A, Hu X, Tam S, Hwang SH, Ingham ES, Kieran MW, Weiss RH, Ferrara KW, Hammock BD. 2013. Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis. Proc Natl Acad Sci U S A 16;110(16):6530-6535.