Berkeley - Those seeking yet another reason to eat their veggies, take note. Researchers at the University of California, Berkeley, have found that a chemical produced when digesting such greens as broccoli and kale can stifle the growth of human prostate cancer cells.
The findings show that 3,3'-diindolylmethane (DIM), which is obtained by eating cruciferous vegetables in the Brassica genus, acts as a powerful anti-androgen that inhibits the proliferation of human prostate cancer cells in culture tests.
"As far as we know, this is the first plant-derived chemical discovered that acts as an anti-androgen," said Leonard Bjeldanes, professor and chair of nutritional sciences and toxicology at UC Berkeley's College of Natural Resources and principal investigator of the study. "This is of considerable interest in the development of therapeutics and preventive agents for prostate cancer."
Vegetables such as broccoli, Brussels sprouts, kale and cauliflower are rich sources of indole-3-carbinol (I3C), which the body converts into DIM during digestion. Over the years, Bjeldanes has been researching the anti-cancer properties of dietary indoles with co-author Gary Firestone, UC Berkeley professor of molecular and cell biology.
The new study will be published in the June 6 issue of the Journal of Biological Chemistry, but is now available online.
Androgen is an important hormone for the normal development and function of the prostate, but it also plays a key role in the early stages of prostate cancer, which is typically treated with anti-androgen drugs.
In most cases of prostate cancer, the cancer cells develop resistance to androgen and grow independently of the hormone in later stages of the disease.
In the new study, the researchers conducted a series of tests comparing the effects of DIM on androgen-dependent human prostate cancer cells as well as on their androgen-independent counterparts.
They found that androgen-dependent cancer cells treated with a solution of DIM grew 70 percent less than the same type of cancer cells that had been left untreated. The same solution had no effect on the growth of androgen-independent cells, pointing to androgen inhibition as the key mechanism by which the DIM is acting.
This was confirmed with further tests showing that DIM inhibits the actions of dihydrotestosterone (DHT), the primary androgen involved in prostate cancer. DHT stimulates the expression of prostate specific antigen (PSA), which acts as a growth factor for prostate cancer. When androgen-dependent cells were treated with DIM, the researchers found a drop in the level of PSA.
"There are lots of things that can stop growth, but the fact that DIM decreases the expression of PSA shows that it is functioning at a gene expression level," said Bjeldanes.
Comparisons of the molecular conformation of DIM show that it is similar to Casodex, a synthetic anti-androgen on the market. "DIM works by binding to the same receptor that DHT uses, so it's essentially blocking the androgen from triggering the growth of the cancer cells," said Hien Le, lead author of the study and a former graduate student in Bjeldanes' lab.
"DIM is chemically different than Casodex, but it behaves similarly in how it blocks the effects of androgen," said Le, who received her PhD in molecular and biochemical nutrition in 2002.
These latest findings appear to add new burnish for this class of chemicals that has already shown promise in prior studies as a therapeutic agent for breast and endometrial cancer. For instance, a 1998 study by Bjeldanes and Firestone showed that I3C keeps breast cancer cells from duplicating.
"We are investigating the potential use of indoles in combination with current anti-cancer drugs on the market," said Firestone. "The advantage of combination therapy is that you can back off on the dose of a single agent and thereby reduce potential side effects."
Prostate cancer is the second leading cause of cancer deaths in American men. One in 10 men in the United States will develop signs of prostate cancer in his life, and more than 100,000 new cases are reported each year.
Le pointed out that the incidence of prostate cancer among men in Asia - where consumption of vegetables is higher - is significantly lower than that for men in the United States. However, the risk for Asian immigrants rises to levels comparable to American men the longer they stay in the United States, suggesting that factors such as diet and lifestyle play a role in the development of prostate cancer.
"There are already plenty of health reasons for consuming more vegetables such as broccoli," said Le. "This study suggests that there are even more benefits to a diet rich in these phytochemicals when it comes to preventing prostate cancer."
The study was also co-authored by Charlene Schaldach, a former PhD student in the Bjeldanes lab.
The research is supported by the California Cancer Research Project and the National Institute of Environmental Health Sciences, part of the National Institutes of Health.
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