Cancer
Broccoli and soy may help prevent breast cancer from spreading
By Ben Wasserman
Apr 16, 2007 - 12:53:26 PM

3,3-Diindolylmethane and genistein found in broccoli and soy respectively may help prevent the spreading of breast cancer and ovarian cancer, according to a study by researchers at the University of California, Los Angeles.

Studies have linked eating such foods as broccoli and soy to reduced risk for some types of cancer, but it is not well understood how these foods could possibly provide such protection against cancer.

In the study, researchers discovered a biological mechanism which explains that diindolylmethane (DIM), a compound resulting from digestion of cruciferous vegetables, and genistein, a major isoflavone in soy prevent the spread of cancer by reducing production of two proteins whose chemotactic attraction to each other is necessary for the spread of breast and ovarian cancers.

When applied to motile cancer cells, purified DIM and genistein significantly reduced cell migration and invasion, according to the study, which was presented at the 2007 Annual Meeting of the American Association for Cancer Research.

"We think these compounds might slow or prevent the metastasis of breast and ovarian cancer, which would greatly increase the effectiveness of current treatments," said Erin Hsu, a graduate student in molecular toxicology. "But we need to test that notion in animals before we can be more definitive."

Both DIM and genistein are being developed for use as a preventive and a chemotherapy treatment for breast cancer, but more extensive toxicological studies are needed, the researchers said.

Purified genistein, a phytochemical that is similar to estrogen, is toxic to organs like ovaries and at high level, it can make mice infertile or subfertile, according to a government study, which was conducted by W Jefferson, E Padilla-Banks, R Newbold and M Pepling ad published in the January 2006 issue of Biology of Reproduction.

In the current study, the researchers examined the effect of DIM and genistein on the "CXCR4/CXCL12 axis," which is known to play a central role in the spreading of breast cancer and the development of ovarian cancer.

CXCR4 chemokine receptors are produced by primary cancer cells on their surface while CXCL 12 chemkine ligands are produced by the organs to which the cancer cells may spread to.    The attraction between the two stimulates the invasive properties of cancer cells and draws the cancer cells to the organs.

Purified DIM or genistein when applied to breast and ovarian cancer cell lines reduced levels of CXCR4 and CXCL12 messenger RNAs and proteins in a dose-dependent manner, according to Hsu.

In the study, the researchers placed the cells in one end of a compartment and watched how they moved toward CXCL12 at the other end with and without DIM or genistein applied.

"The cells degrade the extracellular matrix in the upper compartment in order to move toward CXCL12 in the lower compartment, a system that represents a cell culture model for invasiveness," she said.

However, when the cells were treated with either DIM or genistein, movement toward CXCL12 was reduced by at least 80 percent compared to untreated cells, the researchers said.

The same chemotactic attraction is thought to be the way for more than 23 types of cancer to develop, Hsu said.   The researchers have found that DIM and genistein substantially reduced messenger RNA expression of CXCR4 and CXCL 12 when they were applied to melanoma and prostate cancer cells.

"We have also tested other phytochemicals and seen similar effects, indicating that this mechanism may mediate protective effects of other vegetable products as well," Hsu said.

The researchers said the amount of DIM and genistein used in this study is probably comparable to a high dose of supplements, which can't be achieved through consumption of food alone.