An anti-cancer compound found in broccoli and cabbage works by lowering the activity of an enzyme associated with rapidly advancing breast cancer, according to a University of California, Berkeley, study appearing this week in the online early edition of the journal Proceedings of the National Academy of Sciences.
The compound, indole-3-carbinol, is already undergoing clinical trials in humans because it was found to stop the growth of breast and prostate cancer cells in mice.
The new findings are the first to explain how indole-3-carbinol (I3C) stops cell growth, and thus provides the basis for designing improved versions of the chemical that would be more effective as a drug and could work against a broader range of breast as well as prostate tumors.
"I think one of the real uses of this compound and its derivatives is combining it with other kinds of therapies, such as tamoxifen for breast cancer and anti-androgens for prostate cancer," said coauthor Gary Firestone, UC Berkeley professor of molecular and cell biology. "Humans have co-evolved with cruciferous vegetables like broccoli and Brussels sprouts, so this natural source has a lot fewer side effects."
"This is a major breakthrough in trying to understand what the specific targets of these natural products are," said coauthor Leonard Bjeldanes, UC Berkeley professor of toxicology. "The field is awash with different results in various cells, but no real identification of a specific molecular target for these substances. The beauty of identifying the target like this is that it suggests further studies that could augment the activity of this type of molecule and really specify uses for specific cancers."
Firestone, Bjeldanes and their colleagues showed that I3C inhibits the enzyme elastase, which at high levels in breast cancer cells heralds a poor prognosis: decreased response to chemotherapy, reduced response to endocrine treatment and reduced survival rates.
Elastase is an enzyme that shortens a cellular chemical, cyclin E, that is involved in controlling the cell cycle. The shortened version of cyclin E accelerates the cell cycle, making cancer cells proliferate faster. Firestone showed that I3C prevents the elastase shortening of cyclin E, thereby arresting development of breast cancer cells.
For more than 15 years, Firestone, Bjeldanes and their colleagues have studied the anti-cancer benefits of vegetables in the cabbage family that are lumped together in the genus Brassica and, because of their cross-shaped flowers, are often referred to as cruciferous vegetables.
Though the anti-cancer benefits have been recognized since the 1970s, the mechanism is only now being discovered, in part through the work of Firestone, Bjeldanes and their UC Berkeley colleagues.
"We have connected the dots on one extremely important pathway" by which indole-3-carbinol works, Firestone said.