The findings are being published by researchers from the Linus Pauling Institute at Oregon State University, in Seminars in Cancer Biology, a professional journal. “The traditional view of cancer is that genetic damage and DNA mutations occur, in ways that can turn off key genes and our natural defense mechanisms against cancer,” said Rod Dashwood, a professor of environmental and molecular toxicology and head of LPI’s Cancer Chemoprotection Program. “That clearly is one cause of cancer. But we’re finding out that epigenetic mechanisms can also produce this same effect within cells containing normal, non-mutated DNA.”
In this view of cancer, genetic damage to a cell is less relevant than other forces – which can be the result of toxins, stresses or diet – that have the power to change gene expression in cells that are otherwise undamaged. It has been known for some time that broccoli, for instance, contains anti-carcinogens and can help protect against cancer. In several recent studies, OSU researchers are finding out one reason why. They have been able to trace – first in the cell, then in mouse experiments and finally in human tests – the effects that sulforaphane, one of the key compounds in broccoli and other cruciferous vegetables, has on gene expression. In particular, they showed that sulforaphane may inhibit the activity of histone deacetylases, or HDACs, in human colon and prostate cancer lines. HDACs are a family of enzymes that, among other things, affect access to DNA and play a role in whether certain genes are expressed or not, such as tumor suppressor genes. "Our experiments suggest that HDAC inhibitors can turn on these silenced genes, restore normal cellular function and suppress tumor growth,” says researchers.
They first demonstrated this effect in human colon cancer cells treated with sulforaphane, and then LPI collaborator Emily Ho found the same HDAC inhibition in prostate cancer cells. In studies done with mouse models, tumors were suppressed 50 percent by a diet containing sulforaphane. And then in human experiments, the OSU researchers were able to show a dramatic level of HDAC inhibition immediately following a single serving of broccoli sprouts, rich in sulforaphane. Some cancer drugs have already been developed that take advantage of this HDAC inhibition process, and OSU researchers believe that options are available for cancer prevention or even therapy with certain diets or supplements. Appropriate dietary programs might also serve as a synergistic complement to conventional treatments for cancer.
Other dietary HDAC inhibitors studied by researchers include garlic organosulfur compounds and butyrate – a compound produced in the intestine when dietary fiber is fermented, and providing one possible explanation for why higher intake of dietary fiber might help prevent cancer.
“The health implications of epigenetics are really enormous. The root of many disease processes is aberrant gene or protein expression. To the extent we can learn new ways to affect or change gene expression in desirable ways, through diet or drugs, we may be able to better address not just cancer but many other chronic diseases or health problems as well.” That could include heart disease, stroke, neurodegeneration, Huntington’s disease, epilepsy, bipolar disorder, and aging, the researchers speculated in their report. At least in theory, a single dietary component – whether it’s sulforaphane in broccoli or resveratrol in red wine – might affect a number of disease issues, scientists say.
This field of research is sufficiently new that the first-ever summer conference on HDACs was just held last month. Another such meeting is planned in September, 2007, at the National Institute of Health, with Dashwood as an invited speaker. Studies by Dashwood and Ho are currently supported by the National Cancer Institute, the National Institute of Environmental Health Sciences and the Oregon Agricultural Experiment Station.
Bonnie - does this not sound familiar? We have been talking Epigenetics at Nutritional Concepts since last year. In fact, we recommend dietary and supplemental substances to harmonize our epigentic pathways (i.e. kinases) whenever needed. It is very exciting that the research is beginning to mount!
State of the Nutritionist Speech
Epigenetics Part I: Preventing Chronic Disease.
Epigenetics Part II: First Priority in Preventing Chronic Disease