We all know that eating fruits, vegetables and soy products provides essential nutrition for a healthy lifestyle, while obesity leads to the opposite. Yet proving the effect of nutrition, or obesity, on cancer is an experimental challenge and a focus for scientists. According to emerging evidence being presented at the 2007 Annual Meeting of the American Association for Cancer Research, eating well might still be one of the more pleasurable ways to prevent cancer and promote good health.
Eating such foods as broccoli and soy are believed to offer some protection against cancer, but how this occurs is not well-understood. Now, in laboratory experiments, researchers at the University of California, Los Angeles, have discovered a biological mechanism whereby two compounds in these foods might lower the invasive and metastatic potential of breast and ovarian cancer cells.
They found that diindolylmethane (DIM), a compound resulting from digestion of cruciferous vegetables, and genistein, a major isoflavone in soy, reduce production of two proteins whose chemotactic attraction to each other is necessary for the spread of breast and ovarian cancers.
When applying purified versions of DIM and genistein to motile cancer cells, the researchers could literally watch these cells come to a near halt. When either compound was applied, migration and invasion were substantially reduced.
"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 already being developed for use as a preventive and a chemotherapy treatment for breast cancer, although more extensive toxicological studies are necessary, the researchers say.
The researchers looked at the potential of DIM and genistein to interfere with the "CXCR4/CXCL12 axis," which is known to play a central role in the metastasis of breast cancer and is also thought to play a role in the development of ovarian cancer. Primary cancer cells express very high levels of the CXCR4 chemokine receptor on the surface of their cells, and the organs to which these cancers metastasize secrete high levels of the CXCL12 chemokine ligand. This attraction stimulates the invasive properties of cancer cells and acts like a homing device, drawing the cancer cells to the organs they metastasize to.
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," she said.
But if the cells are treated with either DIM or genistein, movement toward CXCL12 is reduced by at least 80 percent compared to untreated cells, the researchers say.
Hsu says that this same chemotactic attraction is thought to play a role in the development of more than 23 different types of cancer, and, so far, they have found that messenger RNA expression of CXCR4 and CXCL12 is substantially reduced when melanoma and prostate cancer cells are treated with the two compounds.
"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 amount of DIM and genistein used in this study is probably comparable to use of a high dose of supplements, and is likely not achievable through consumption of food alone, the researchers say.
The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, diagnosis and treatment. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.
Eating such foods as broccoli and soy are believed to offer some protection against cancer, but how this occurs is not well-understood. Now, in laboratory experiments, researchers at the University of California, Los Angeles, have discovered a biological mechanism whereby two compounds in these foods might lower the invasive and metastatic potential of breast and ovarian cancer cells.
They found that diindolylmethane (DIM), a compound resulting from digestion of cruciferous vegetables, and genistein, a major isoflavone in soy, reduce production of two proteins whose chemotactic attraction to each other is necessary for the spread of breast and ovarian cancers.
When applying purified versions of DIM and genistein to motile cancer cells, the researchers could literally watch these cells come to a near halt. When either compound was applied, migration and invasion were substantially reduced.
"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 already being developed for use as a preventive and a chemotherapy treatment for breast cancer, although more extensive toxicological studies are necessary, the researchers say.
The researchers looked at the potential of DIM and genistein to interfere with the "CXCR4/CXCL12 axis," which is known to play a central role in the metastasis of breast cancer and is also thought to play a role in the development of ovarian cancer. Primary cancer cells express very high levels of the CXCR4 chemokine receptor on the surface of their cells, and the organs to which these cancers metastasize secrete high levels of the CXCL12 chemokine ligand. This attraction stimulates the invasive properties of cancer cells and acts like a homing device, drawing the cancer cells to the organs they metastasize to.
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," she said.
But if the cells are treated with either DIM or genistein, movement toward CXCL12 is reduced by at least 80 percent compared to untreated cells, the researchers say.
Hsu says that this same chemotactic attraction is thought to play a role in the development of more than 23 different types of cancer, and, so far, they have found that messenger RNA expression of CXCR4 and CXCL12 is substantially reduced when melanoma and prostate cancer cells are treated with the two compounds.
"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 amount of DIM and genistein used in this study is probably comparable to use of a high dose of supplements, and is likely not achievable through consumption of food alone, the researchers say.
The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes more than 25,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts over 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, diagnosis and treatment. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship and advocacy.
