An omega-6 fatty acid known as arachidonic acid turns on a gene signaling pathway that leads directly to tumor growth, according to principal investigator Millie Hughes-Fulford, PhD, director of the Laboratory of Cell Growth at SFVAMC and scientific advisor to the U.S. Under Secretary for Health for the Department of Veterans Affairs.
The results of the study are published in the February 1 issue of Cancer Research.
"After we added omega-6 fatty acids to the growth medium in the dish, and only omega-6, we observed that tumors grew twice as fast as those without omega-6," recounts Hughes-Fulford, who is also an adjunct professor of medicine at the University of California, San Francisco.
"Investigating the reasons for this rapid growth, we discovered that the omega-6 was turning on a dozen inflammatory genes that are known to be important in cancer. We then asked what was turning on those genes, and found that omega-6 fatty acids actually turn on a signal pathway called PI3-kinase that is known to be a key player in cancer," she adds.
Hughes-Fulford says the results are significant because of the high level of omega-6 fatty acids in the modern American diet, mostly in the form of vegetable seed oils such as corn oil--over 25 times the level of beneficial omega-3 fatty acids, which are found in canola oil, fish, and green vegetables. She notes that over the last 60 years, the rate of prostate cancer in the U.S. has increased steadily along with intake of omega-6, suggesting a possible link between diet and prostate cancer.
The study results build on earlier work in which Fulford and her research team found that arachidonic acid stimulated the production of an enzyme known as cPLA-2, which in turn caused a chain of biochemical reactions that led to tumor growth. In the current paper, the researchers have "followed that biochemical cascade upstream to its source," Hughes-Fulford says. "These fatty acids are initiating the signal pathway that begins the whole cascade."
Hughes-Fulford and her fellow researchers also found that if they added a non-steroidal antiflammatory or a PI3K inhibitor to the growth media, interrupting the signal pathway, the genes did not get turned on and increased tumor cell growth did not take place.
Currently, Hughes-Fulford is conducting a study in which research animals are fed diets with different levels of omega-3 and omega-6 fatty acids, "to see how the tumors grow in animals."
Hughes-Fulford says that her study results have directly influenced her own diet. "I'm not a physician, and do not tell people how to eat, but I can tell you what I do in my own home," she says. "I use only canola oil and olive oil. We do not eat deep-fried foods."
Co-authors of the study include Chai-Fei Li, BA, of the Northern California Institute for Research and Education, J.B. Boonyaratanakornkit, BS, of SFVAMC and UCSF, and Sina Sayyah, BA, of NCIRE.
The study was funded by grants from the Department of Veterans Affairs and a grant from NASA that was administered by NCIRE.
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Journal
Cancer Research