How the Phytochemical Indole-3-Carbinol Disrupts Cancer Growth

They found that treatment of highly invasive MDA-MB-231 breast cancer cells with I3C shifted the stable accumulation of cyclin E protein from the lower molecular weight 35-kDa form that is associated with cancer cell proliferation and poor clinical outcomes to the higher molecular weight 50-kDa cyclin E form that typically is expressed in normal mammary tissue. Cyclin E is a protein involved in controlling the cell cycle, and the lower molecular weight version of cyclin E accelerates the cell cycle, making cancer cells proliferate faster.

Data presented in a paper published in the December 8, 2008, online edition of the journal Proceedings of the [U.S.] National Academy of Sciences (PNAS), revealed that I3C had a direct inhibitory effect on the enzyme elastase, which crops the benign higher molecular weight form of cyclin E and transforms it into the pathogenic lower molecular weight form.

Elastase also breaks down elastin, an elastic fiber that together with collagen determines the mechanical properties of connective tissue. Thus, the inhibitory action of I3C also disrupts cancer cell migration and alters the adhesion properties of cancer cells.

"We have connected the dots on one extremely important pathway by which indole-3-carbinol works,” said senior author Dr. Gary Firestone, professor of molecular and cell biology at the University of California. "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. Humans have coevolved with cruciferous vegetables like broccoli and Brussels sprouts, so this natural source has a lot fewer side effects.”

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