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 r
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Contact: Sarah Yang
scy@pa.urel.berkeley.edu
510-643-7741
University of California - Berkeley
15-May-2003