Prostate cancer remains the most common malignancy among U.S. men, and internationally it ranks fourth. Though few studies have offered much insight into what triggers this disease, a growing number of researchers have found evidence suggesting that dietary selenium protects men against this cancer.

Indeed, a February 2003 paper in the International Journal of Cancer found that among 445 U.S. men, high blood concentrations of selenium appeared to reduce by 30 percent the risk that a man would develop prostate cancer.

Selenium is a constituent of the enzyme glutathione peroxidase, one of the body's more potent antioxidants. Such agents have the ability to quash biologically damaging reactions triggered within the body by any of a host of naturally produced chemicals called oxidants.

Because oxidant damage has been linked with many cancers, some scientists have suspected that any anticancer benefit from selenium probably would trace to its antioxidant contribution.

In fact, however, several new studies suggest that at least one of the nutrient's primary anticancer benefits may be its protection or repair of a suicide switch in genetically damaged cells. It's when the body allows this switch to fail that cancer's runaway growth occurs.

Dogging the problem

David J. Waters of Purdue University and his colleagues were the first to report this discovery in a study of prostate health in elderly beagles. They chose these dogs because, like men, this species spontaneously develops prostate cancer at rates that increase with age.

For 7 months, the scientists supplemented the diets of 38 male dogs — animals physiologically equivalent to 65-year-old men — with either of two dietary supplements: selenomethionine or high-selenium yeast. Another 10 dogs received a similar diet but no extra selenium.

At the end of the trial, the researchers sampled blood from each of the animals and then sacrificed the dogs to examine their prostate glands.

Cancers typically trace to DNA damage, and Waters' team found far less of it in the white blood cells and the prostate tissue of dogs treated with selenium than in the untreated group. For instance, 79 percent of the prostate cells examined from untreated dogs had "extensive DNA damage" compared with just 57 percent of such cells from dogs getting supplemental selenium.

However, Waters and his colleagues report in the Feb. 5 Journal of the National Cancer Institute that the degree of DNA protection bore no relationship to the activity of glutathione peroxidase in those tissues. "In other words," Waters told Science News Online, "[selenium's] beneficial effects cannot be explained by the fact that it was pushing antioxidant enzymes higher."

So how does selenium protect the prostate? It may be by controlling the selective culling of cells with damaged DNA.

Helping cancer cells die

Normally, cells develop, grow old, and then die. Cancer cells, however, don't die naturally. Like Methuselah, they seem immortal and continue to produce endless progeny throughout their long lives.

Cancer cells would pose far less of a problem if the normal suicide switch within them could be reactivated. Such programmed cell death is known as apoptosis. Interestingly, Waters' team found roughly twice the level of apoptosis occurring within the prostate tissue of selenium-supplemented dogs as in untreated beagles. In fact, hot spots of apoptosis appeared in 16 of the 38 treated beagles (42 percent) but just one of the 10 dogs from the untreated group.

The elevated apoptosis in the selenium-treated animals could put a break on the development of prostate malignancies. "The idea here," explains Waters, who also holds a research appointment at the Seattle-based Gerald P. Murphy Cancer Foundation, "is that the cells that are most DNA damaged — and presumably have the highest propensity to turn cancerous — may be selectively purged in the presence of [supplemental] selenium."

The supplementation that conferred this protection was anything but massive. Half the dogs receiving each supplement got a low dose — just 50 percent more than typically occurs in a dog-chow diet and the rest got double the normal dietary selenium supply.

"These are really nontoxic doses," Waters emphasizes. In fact, the lower supplemental dose was roughly equivalent to 200 micrograms per day in men. That's the same amount being administered to some people taking part in a massive, 12-year National Cancer Institute (NCI) nutrition trial. What's more, the forms of selenium tested in the dogs are identical to the forms given to men in earlier trials. In fact, the NCI trial is using selenium methionine.

In the dog trial, the two forms of selenium appeared equally protective, and the low doses were just as good as the high doses.

Why did the Purdue researchers test agents that already have shown their value in people? "Because we want to understand the mechanisms," Waters says, which may point to better doses, the chemical forms that perform best, the ideal timing for supplementation, and whether there will be deleterious interactions between the supplements and drugs or other nutrients in the diet.

Even broccoli may help

John W. Finley and his colleagues at the Agricultural Research Service's Human Nutrition Research Center in Grand Forks, N.D., have been probing a more natural selenium supplement. They aim to deliver anticancer benefits from selenium by enriching the nutrient's concentrations in broccoli.

At the Experimental Biology 2003 meeting in San Diego last week, Finley's group reported data from mice that spontaneously develop precancerous tissue in their digestive tract. Animals downing high concentrations of the novel broccoli developed several anticancer changes — among them, the activation of apoptosis-promoting genes.

In another paper at the same meeting, Aimee L. Taylor and her colleagues at Brigham Young University in Provo, Utah, provided data from test-tube studies of prostate cancer cells treated with high concentrations of selenium. Here, too, the nutrient inhibited a series of genes that can turn off the molecular suicide switch in cancer cells.

Looking for other natural sources of this trace mineral? Try seafood, organ meats such as kidney and liver, and to a lesser extent, other meats. Though some grains can be rich stores of selenium, whether they do depends on the mineral status of the soil in which they're grown.

References and Sources

References:

2001. Selenium and vitamin E cancer prevention trial (SELECT): Questions and answers. National Cancer Institute. Oct. 29. Available here.

1996. Selenium supplements lower incidence of lung, colorectal, and prostate cancers. National Cancer Institute press release. Dec. 24. Available here.

Taylor, A.L., E.T. Nartey, and M.J. Christensen. 2003. High selenium reduces NF-kB-regulated gene expression in human prostate cancer cells. Experimental Biology 2003 meeting. April 11-15. San Diego.

Vogt, T.M., et al. 2003. Serum selenium and risk of prostate cancer in U.S. blacks and whites. International Journal of Cancer 103(Feb. 20):664-670.

Waters, D.J., et al. 2003. Effects of dietary selenium supplementation on DNA damage and apoptosis in canine prostate. Journal of the National Cancer Institute 95 (Feb. 5):237-241. Abstract available here.

Zeng, H., C.D. Davis, and J.W. Finley. 2003. Effect of selenium-enriched broccoli diet on differential gene expression in Min mouse liver. Experimental Biology 2003 meeting. April 11-15. San Diego.

Further Readings:

Raloff, J. 2001. Anticancer mineral works best in food. Science News 159(April 21):248. Available to subscribers here.

Radical prostates. Science News 151(Feb. 22, 1997):126. Available here.
Seppa, N. 1998. Can selenium avert prostate cancer? Science News 154(Sept. 19):188. References and sources available here.

Sources:

David J. Waters
School of Veterinary Medicine
Purdue University
625 Harrison Street
West Lafayette, IN 47907-2026

Gerald P. Murphy Cancer Foundation
13758 Lake City Way NE, Suite 200
Seattle, WA 98125-3699

From Science News, Vol. 163, No. 18, May 3, 2003, p.
© 2003 Science Service.