Eating foods like broccoli and soy has been linked to lower cancer rates, and California researchers say that they may have discovered what underlies this protective effect. Using cells in a lab dish, a team led by Erin Hsu, a graduate student in molecular toxicology at the University of California, Los Angeles has found that genistein, an isoflavone in soy, and diindolymethane (DIM), a compound made in the gut when broccoli is digested, reduce the production of two proteins needed for cancers to spread.
Previous research has suggested that risk of prostate cancer may be reduced by dietary intake of DIM from broccoli and genistein from soy. Erin Hsu (left), who led this study says it’s the first to find a clue to the value of dishes in which broccoli or other cruciferous vegetables like kale, bok choy, brussel spouts and cabbage are served with soy foods like tofu and edamame beans.
Research in the past 5 years has shown that interaction between two small proteins called chemokines, CXCL12–CXCR4, causes prostate cancer cells to spread. But it had not been shown before that dietary intake of DIM and genistein might impact cancer spread and do so by blocking signals between these chemokines.
Chemokines are important in directional migration of cancer cells and evidence suggests that they are involved in many stages of tumor development and progression.
This new research, while focused on breast and ovarian cancer cells, jumps off from a previous finding that messenger RNA expression of CXCR4 and CXCL12 is substantially reduced when melanoma and prostate cancer cells are treated with the broccoli DIM and soy genistein.
Cancer cells express very high levels of a surface receptor known as CXCR4, while the organs to which the cancers spread secrete high levels of CXCL12, a ligand that binds to that particular receptor.
Attraction between CXCR4 and CXCL12 causes cancer cells to travel. The attraction acts like a homing device, signaling cancer cells away from primary tumors to distant organs like the liver or brain.
Erin Hsu says that this chemotactic attraction is thought to play a role in the development of more than 23 different types of cancer.
The study performed by Hsu’s team found that when cancer cells were treated with either DIM or genistein, movement toward CXCL12 is reduced by at least 80 percent compared to untreated cells.
When breast and ovarian cancer cell lines are exposed to purified DIM or genistein, levels of CXCR4 and CXCL12 messenger RNAs and proteins decrease in a dose-dependent manner, compared to untreated cells, according to Hsu.
To assess whether the compounds had any effect on the metastatic potential of the cells, the researchers placed the cells in one end of a compartment and watched how they moved toward CXCL12 at the other end. “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,” Hsu said.
“We think these compounds might slow or prevent the metastasis of breast and ovarian cancer, which would greatly increase the effectiveness of current treatments,” she said.
The UCLA team, which reported its finding at a meeting of the American Association for Cancer Research, will next test the theory in mice.
The findings highlight “an entirely unique mechanism … Preventing the invasion and metastasis of cancer cells is crucial,” said Dr. Alan Kristal, associate head of the cancer prevention program at Fred Hutchinson Cancer Research Center in Seattle.
The amount of DIM and genistein used in the study is probably comparable to use of a high dose of supplements, and is likely not achievable through consumption of food alone, the researchers said.
“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.
Both DIM and genistein are already being developed for use as a preventive, and a chemotherapy treatment for breast cancer, although more extensive toxicological studies are needed, they added.
References
The importance of the CXCL12-CXCR4 chemokine ligand-receptor interaction in prostate cancer metastasis. Arya, M et al. Prostate Cancer Research Centre, Institute of Urology, University College London, UK. J Exp Ther Oncol. 2004 Dec;4(4):291-303.
CXCL12–CXCR4 interactions modulate prostate cancer cell migration, metalloproteinase expression and invasion
Shailesh Singhet al. Morehouse School of Medicine, Atlanta, GA, USA, University of Alabama at Birmingham, Birmingham, AL, USA
Laboratory Investigation (2004) 84, 1666–1676
What’s edamame and can you grow edamame from seed?
Edible soybean, called Edamame (eh-dah-MAH-may) meanaing meaning “branched bean” in Japan and Mao Dou in China, can be grown from seed. Here’s one supplier of Asian vegetable seeds and a page about edamame.
In the USA special agricultural projects are underway to grow edamame in places like Colorado. All you really need to know is where to find edamame in the frozen vegetable section in the supermarket. Companies including Cascadian Farms sell frozen edamame.
