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Broccoli compound targets enzyme in late-stage cancer

December 15, 2008 — 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.

December 15, 2008 — 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.

The study appeared December 3 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.

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.

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.

In previous work, they found that indole-3-carbinol interferes with more than cell proliferation. It also disrupts the migration and alters adhesion properties of cancer cells, as well as counteracts the survival ability of cancer cells, all of which are implicated in cancer cell growth. To have such broad downstream effects, I3C must act at the beginning of a major cellular pathway, Firestone said. The newly reported research pins this activity to elastase and its effect on cyclin E.

Bjeldanes noted that I3C is available as a supplement and is a preferred preventative treatment for recurrent respiratory papillomatosis, a condition involving non-malignant tumors of the larynx. Improved versions of the chemical could thus help treat cancers other than those of the breast and prostate.