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07-25-07

Media Release

‘Epigenetics’ Providing a New View of Diet and Cancer

CORVALLIS, Ore. – A new study concludes that one of the ways diet may help prevent or treat cancer is through its impact on gene expression – influencing which genes are turned “on” or “off.”

This “epigenetic” view of cancer is quite new, researchers say in the report, and may help explain not only how some cancers form and progress, but also provide new approaches to their treatment and prevention, either through drugs or diet. And the impact of the discoveries could be relevant to other disease processes as well, ranging from cardiovascular disease to epilepsy and bipolar disorder.

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.

“In healthy cells, there are mechanisms to prevent inappropriate cellular growth, and these mechanisms are circumvented in cancer cells” Dashwood said. “Tumor suppressor genes can be turned off either by mutation at the genetic level, or dysregulated by environmental factors, leading to cancer. But our experiments suggest that HDAC inhibitors can alter histone acetylation patterns, which influences DNA accessibility. This can turn on these silenced genes, restore normal cellular function and suppress tumor growth.”

Dashwood 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, with further research, more options should be made 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, Dashwood said.

Other dietary HDAC inhibitors studied by Dashwood 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,” Dashwood said. “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.

About the Linus Pauling Institute: The Linus Pauling Institute at OSU is a world leader in the study of micronutrients and their role in promoting optimum health or preventing and treating disease. Major areas of research include heart disease, cancer, aging and neurodegenerative disease.