Brown MD, Hart CA, Gazi E, et al. Promotion of prostatic metastatic migration towards human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs. Br J Cancer, 2006;94(6):842-853.

Epidemiological studies have shown not only a relationship between the intake of dietary lipids and an increased risk of developing metastatic prostate cancer, but also the type of lipid intake that influences the risk of metastatic prostate cancer.

The Omega-6 poly-unsaturated fatty acid, Arachidonic acid, has been shown to enhance the proliferation of malignant prostate epithelial cells and increase the risk of advanced prostate cancer. However, its role in potentiating the migration of cancer cells is unknown.

Here we show that arachidonic acid at concentrations 5 M is a potent stimulator of malignant epithelial cellular invasion, which is able to restore invasion toward hydrocortisone-deprived adipocyte-free human bone marrow stroma completely.

This observed invasion is mediated by the arachidonic acid metabolite prostaglandin E2 and is inhibited by the Omega-3 poly-unsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid at a ratio of 1 : 2 Omega-3 : Omega-6, and by the COX-2 inhibitor NS-398.

These results identify a mechanism by which arachidonic acid may potentiate the risk of metastatic migration and secondary implantation in vivo, a risk which can be reduced with the uptake of Omega-3 poly-unsaturated fatty acids.

Every man wants to reduce his risk of prostate cancer. At present, the evidence points to diet as the best way (see Harvard Men's Health Watch, March 2001). The most important step is to reduce your intake of saturated fat from animal sources such as red meat and whole dairy products. Foods that may help include tomatoes and other vegetables, soy, whole grains, nuts, and seeds. But although people can live very nicely on vegetables alone, few men choose this course. Happily, two new studies add an animal food to the "good" column not a land animal, but one that lives in the water. In fact, the fish that help the most are the ones that live in the deepest, coldest water.

Fishing for protection
Scientists in Sweden investigated the possible benefits of fish by studying 6,272 men with an average age of 56 when the study began in 1967. Each man provided detailed information about his diet as well as his smoking, drinking, and exercise habits. During a 30-year observation period, 466 men were diagnosed with prostate cancer and 340 died from the disease.
When the scientists compared the men who developed prostate cancer with those who did not, they found that eating fish was associated with protection. Men who ate moderate to large amounts of fish had only a third to half the risk of prostate cancer as the others.
The men who ate the most fish also ate the most vegetables and the least meat. In addition, they got more exercise and smoked less. But fish remained protective even after other dietary and lifestyle factors were considered. In fact, multivariate risk factor analysis actually bolstered the statistical evidence that favored fish. And since the men in the study were all members of the Swedish Twin Registry, the researchers were able to determine that genetic and environmental factors did not bias the results.

Harvard agrees
Earlier this year, Harvard's Health Professionals Follow-Up Study reported that fish appear protective on both sides of the Atlantic. In this 12-year study of 47,882 men, eating fish more than three times a week was linked to a reduced risk of prostate cancer. And the apparent benefit was greatest for widespread, aggressive prostate cancer, which occurred 44% less often in the men who ate large amounts of fish than in those who rarely did.

Why fish?
What's so special about fish? The answer is fat. It may seem paradoxical, but it's not. Instead of the harmful saturated fats found in meat and milk, fish have two unique omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA; see HMHW, May 2000). Laboratory experiments suggest these fats may be able to slow the growth of prostate cancer cells. And since the men in the Swedish study ate fish from cold, deep northern waters, they consumed species with large amounts of EPA and DHA, such as salmon, mackerel, and herring.

Perspective
Man cannot live on fish alone. But add whole grains, nuts and seeds, soy, vegetables, and fruits, and you'll have an excellent diet. It's a style of eating that should decrease your risk of prostate cancer ? and even if it doesn't live up to that very realistic expectation, it's sure to reduce your risk of heart attack and sudden cardiac death. Not bad for a diet that also tastes good.

Source: http://www.health.harvard.edu/article.cfm?id=193

News-Medical.Net

Omega-6 fatty acids promote the growth of prostate tumor cells in the laboratory

A study conducted at the San Francisco VA Medical Center (SFVAMC) has demonstrated that omega-6 fatty acids such as the fat found in corn oil promote the growth of prostate tumor cells in the laboratory.

The study also identifies a potential new molecular target for anti-tumor drugs: an enzyme known as cPLA2, which plays a key role in the chain leading from omega-6 fatty acids to prostate tumor cell growth.

The study was led by Millie Hughes-Fulford, PhD, 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. It is being published in the September 2005 issue of Carcinogenesis.

Working with human prostate cancer cells in tissue culture, Hughes-Fulford and her fellow researchers 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 stimulates the release of PGE2, a hormone-like molecule that promotes 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," says 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 points out 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 U.S. has increased steadily.

Hughes-Fulford also found that flurbiprofen, a non-steroidal anti-inflammatory drug commonly prescribed for arthritis, blocked the production of cPLA2 and broke the chain leading to cell growth. This means, she says, 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," she notes. "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."

Hughes-Fulford points out that cPLA2 inhibitors would avoid the problems inherent in the class of drugs known as COX2 inhibitors. These drugs have been shown to be effective against tumor growth as well as in treating the pain associated with inflammatory conditions such as arthritis, but have been implicated in increased risk of cardiovascular problems in people 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 explains.

In future research, Hughes-Fulford will be looking at the overall effect of different types of fatty acids on different tumor types in cell lines as well as human biopsies.

She plans a study that will correlate type of fatty acid with tumor stage and grade in order to obtain a clearer picture of specific effects of different fats on tumor progression.

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.

Source: http://www.news-medical.net/?id=12176