A study conducted at the San Francisco VA Medical Center (SFVAMC)has demonstrated that omega-6 fatty acids such as the fat found in cornoil promote the growth of prostate tumor cells in the laboratory. Thestudy also identifies a potential new molecular target for anti-tumordrugs: an enzyme known as cPLA2, which plays a key role in the chainleading from omega-6 fatty acids to prostate tumor cell growth.
The study was led by Millie Hughes-Fulford, PhD, director of theLaboratory of Cell Growth at SFVAMC and scientific advisor to the U.S.Undersecretary of Health for the Department of Veterans Affairs. It isbeing published in the September 2005 issue of Carcinogenesis, and iscurrently available online.
Working with human prostate cancer cells in tissue culture,Hughes-Fulford and her fellow researchers identified for the first timea direct chain of causation: When introduced into prostate tumor cellsin culture, omega-6 fatty acid causes the production of cPLA2, whichthen causes the production of the enzyme COX2. In turn, COX2 stimulatesthe release of PGE2, a hormone-like molecule that promotes cell growth.
"What's important about this is that omega-6 fatty acids are foundin corn oil and most of the oils used in bakery goods," saysHughes-Fulford, who is also an adjunct professor of medicine at theUniversity of California, San Francisco (UCSF). "Which means that ifyou're eating a diet high in omega-6 fatty acids, it's possible thatyou're turning on this cancer cascade, which has been shown to be acommon denominator in the growth of prostate, colorectal, and somebreast cancers."
The study points out that 60 years ago in the United States, thedietary ratio of omega-6 to omega-3, a beneficial fatty acid, was 1 to2. Today, the ratio is 25 to 1. Over that same 60 years, the incidenceof prostate cancer in the U.S. has increased steadily.
Hughes-Fulford also found that flurbiprofen, a non-steroidalanti-inflammatory drug commonly prescribed for arthritis, blocked theproduction of cPLA2 and broke the chain leading to cell growth. Thismeans, she says, that new drugs might be developed that couldspecifically target cPLA2 and prevent COX2 from being released.
"COX2 has been implicated in the growth of many types of tumors,"she notes. "So if you can find a way to block that cascade in thetumor, starting with cPLA2, you might have a new way of modifying orslowing tumor growth."
Hughes-Fulford points out that cPLA2 inhibitors would avoid theproblems inherent in the class of drugs known as COX2 inhibitors. Thesedrugs have been shown to be effective against tumor growth as well asin treating the pain associated with inflammatory conditions such asarthritis, but have been implicated in increased risk of cardiovascularproblems in people who take them regularly. "COX2 inhibitors alsoinhibit prostacyclins, which are enzymes that are beneficial to theheart, and cPLA2 inhibitors would not affect those," she explains.
In future research, Hughes-Fulford will be looking at the overalleffect of different types of fatty acids on different tumor types incell lines as well as human biopsies. She plans a study that willcorrelate type of fatty acid with tumor stage and grade in order toobtain a clearer picture of specific effects of different fats on tumorprogression.
Co-authors of the study were Raymond R. Tjandrawinata, PhD, of UCSF,Chai-Fei Li, BA, of SFVAMC, and Sina Sayyah, BA, of SFVAMC and UCSF.
The research was funded by awards from the U.S. Department ofVeterans Affairs and in part by grants from the National Aeronauticsand Space Administration. Funding was administered by the NorthernCalifornia Institute for Research and Education (NCIRE).
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