Omega-6 Fatty Acids Promote Prostate Cancer

The study, performed at the San Francisco Veteran's Administration Medical Center (SFVAMC; CA, USA), also identified a possible new molecular target for anti-tumor agents: an enzyme calledcPLA2, which plays a major role in the chain leading from omega-6 fatty acids to prostate tumor cell growth.

The study, led by Millie Hughes-Fulford, Ph.D., director of the Laboratory of Cell Growth at SFVAMC and scientific advisor to the U.S. Undersecretary of Health for the Department of Veterans Affairs, was published in the September 2005 issue of the journal Carcinogenesis.

Working with human prostate cancer cells in tissue culture, Dr. Hughes-Fulford and coworkers identified for the first time a direct chain of causation. When introduced into prostate tumor cells in culture, omega-6 fatty acid causes the production of cPLA2, which then causes the production of the enzyme COX2. In turn, COX2 triggers the release of PGE2, a hormone-like molecule that stimulates cell growth.

"What's important about this is that omega-6 fatty acids are found in corn oil and most of the oils used in bakery goods,” said Dr. Hughes-Fulford, who is also an adjunct professor of medicine at the University of California, San Francisco (UCSF). "Which means that if you're eating a diet high in omega-6 fatty acids, it's possible that you're turning on this cancer cascade, which has been shown to be a common denominator in the growth of prostate, colorectal, and some breast cancers.”

The study also noted that 60 years ago in the United States, the dietary ratio of omega-6 to omega-3, a beneficial fatty acid, was 1 to 2. Today, the ratio is 25 to 1. Over that same 60 years, the incidence of prostate cancer in the United States has steadily increased. The researchers also discovered that flurbiprofen, a non-steroidal anti-inflammatory drug typically prescribed for arthritis, blocked the production of cPLA2 and disrupted the chain leading to cell growth. The researchers reported that this means that new drugs might be developed that could specifically target cPLA2 and prevent COX2 from being released.

"COX2 has been implicated in the growth of many types of tumors,” Dr. Hughes-Fulford noted. "So if you can find a way to block that cascade in the tumor, starting with cPLA2, you might have a new way of modifying or slowing tumor growth.”

Dr. Hughes-Fulford pointed out that cPLA2 inhibitors would eliminate the problems inherent in the class of drugs known as COX2 inhibitors. These medications have been shown to be effective against tumor growth as well as in treating the pain associated with inflammatory disorders such as arthritis, but have been implicated in increased risk of cardiovascular problems in individuals who take them regularly. "COX2 inhibitors also inhibit prostacyclins, which are enzymes that are beneficial to the heart, and cPLA2 inhibitors would not affect those,” she explained.

In future studies, Dr. Hughes-Fulford will be researching the overall effect of different kinds of fatty acids on different tumor types in cell lines as well as human biopsies. She also plans a study that will compare type of fatty acid with tumor stage and grade to obtain a clearer outlook on the specific effects of different fats on tumor progression.