Vitamin E Makes Prostate Cancer Cells Vulnerable
Rochester NY, 28 May 2002

Vitamin E, a compound suspected of playing a role in preventing prostate cancer, interferes with two proteins that play a central role in the development of the disease, say scientists at the University of Rochester Medical Center who report their findings in the May 28 issue of the Proceedings of the National Academy of Sciences.

Researchers led by Shuyuan Yeh, PhD, assistant professor in the departments of Urology and Pathology, found that vitamin E interferes with the ability of prostate cancer cells to make both prostate-specific antigen (PSA) and the androgen receptor, a key player in the development and progression of the disease. The work shows that the cancer cells are vulnerable in a way previously unknown.

Yeh showed that in prostate cancer cells exposed to vitamin E, the PSA level drops significantly, as much as 80 to 90 percent, a sign of slowed cancer cell growth. Researchers also saw a 25 to 50 percent decrease in the number of cancer cells, and under certain conditions the compound killed off 90 percent of cancer cells.

While the research was done in the laboratory and not in humans, it takes on added significance because studies in people have already shown that the compound may help prevent prostate cancer. In a study of 29,000 men in Finland, for instance, men who took the vitamin had about one-third fewer cases of prostate cancer than men who did not. But just how the compound might play a protective role has been unclear, making it difficult to study or develop new treatments that might mimic the vitamin's effect.

Since vitamin E is a known anti-oxidant that destroys harmful molecules known as free radicals, some scientists have hypothesized that its anti-oxidant properties might help prevent prostate cancer.

But Yeh's team found that Vitamin E plays an unexpected role in prostate cells. The compound has a dramatic effect on the androgen receptor, a protein in the body that is vital to the growth of prostate cells, including its cancer cells. Researchers found that vitamin E blocks the assembly of the protein, exposing a new vulnerability in a protein that is central to the development of the disease.

The finding gives scientists a new lead to follow when targeting prostate cancer. Currently many of the drugs used to treat prostate cancer either stop the production of testosterone or are "anti-androgens" that prevent testosterone from binding to the androgen receptor, thus stopping the receptor from contributing to cell growth and health. The new research suggests a way to disable the receptor itself. It's a bit like finding a new way to cut off an engine's fuel supply: One could stop the flow of gasoline, or one could simply remove or disable the fuel tank.

Perhaps someday instead of cutting off a man's testosterone supply to prevent the androgen receptor from supporting prostate cancer cells, as they do now, doctors will disable the androgen receptor itself, much like vitamin E does. Or they might combine the approaches. The team found that one traditional anti-androgen drug, hydroxyflutamide, had little effect on the human metastatic prostate cancer cells tested in their study. But when vitamin E was added to the mix, cancer cell growth slowed dramatically.

"This is exciting and quite promising, but until we do further studies in people, we can't really recommend that every man take vitamin E to prevent the disease," says Edward Messing, a co-author and professor and chair of the Department of Urology. Other authors on the paper include graduate students Yu Zhang and Jing Ni; high school student Eugene Chang of Pittsford Sutherland High School; and Chin-Rang Yang, PhD, of the Department of Radiation Oncology.

The scientists also caution that different forms of vitamin E produce different results. The team found that a type known as vitamin E succinate, also known as alpha-tocopheryl succinate, was most effective in halting prostate cancer cells in the laboratory.

"There are several different kinds of vitamin E, and they have different effects. Which type you're talking about makes a very big difference," says Yeh, whose research project was funded by the National Institutes of Health and the Department of Urology. Yeh has worked closely with Rochester scientist Chawnshang Chang, who discovered the androgen receptor.

In the future, Yeh and Messing hope to study the effects of the vitamin in patients with prostate cancer. The team will also continue to study why some forms of the compound are more effective than others in killing cancer cells. Finally, Yeh is studying vitamin D, another compound that has been bandied about for its alleged role in preventing prostate cancer. Yeh's team has found that vitamins D and E may somehow work in concert, with vitamin E helping to boost the effectiveness of vitamin D in killing cancer cells.

Messing is also heading the local portion of a separate study designed to test whether either vitamin E or selenium, or a combination, prevents the disease. The SELECT trial (Selenium and Vitamin E Cancer Prevention Trial) is the largest clinical trial yet of prostate cancer, a disease which strikes about the same number of men -- approximately 200,000 -- as the number of women in the United States who get breast cancer. Prostate cancer is the second-leading cause of death from cancer among men.

Source

University of Rochester.