Eat your veggies: Indirect anti-oxidants provide long-term protection

February 04, 2002

A cancer-preventing compound in broccoli, first isolated a decade ago at Hopkins, may prove to protect against a much broader spectrum of diseases. A new study shows that the compound, sulforaphane, helps cells defend themselves for days against highly reactive and toxic molecules called oxidants.

Unlike standard anti-oxidants that use the molecular equivalent of hand-to-hand combat, broccoli's compound is a covert operative that works indirectly. Oxidants are like molecular hit men, damaging DNA and killing cells, eventually leading to cancer, retinal degeneration, atherosclerosis and other conditions unless they are neutralized.

It turns out that sulforaphane's anti-cancer properties and its indirect anti-oxidant effects are both due to its ability to make cells create a diverse group of enzymes, called "phase 2" enzymes, that protect against cancer by blocking select chemicals from becoming carcinogens. Not previously considered oxidant fighters, the enzymes have the ability to detoxify oxidants, which increases their value in disease prevention, says Talalay.

"Our work with sulforaphane has focused on cancer, but now it assumes wider significance for human disease because the compound also helps prevent oxidative damage," says Paul Talalay, M.D., J.J. Abel Distinguished Service Professor of Pharmacology. "The finding that a compound from the diet can provide powerful, chemically versatile and prolonged protection against oxidative stress may particularly impact human retinal disease."

Studying a variety of cell types and oxidants in laboratory experiments, the scientists discovered that sulforaphane triggers a cellular response that protects cells against oxidants for two or three days, according to a report of the work in the Dec. 16 issue of the Proceedings of the National Academy of Sciences.

"There are many dangers to cells, and it makes sense that cells have protection against these dangers, which include oxidants," says Talalay, who has investigated the link between diet and disease for more than two decades. "Elevating these intrinsic protection mechanisms by administering a wide variety of chemicals, many of which are in the diet already, can be an effective way to prevent disease."

It's now widely recognized that diet influences the risk of diseases including cancer, diabetes, cardiovascular disease and stroke. Anti-oxidants have been one of the most promising dietary strategies for preventing disease, particularly as oxidative damage is linked to more conditions, from cancer to blindness.

As long ago as 1952, blindness resulting from damage to the retina -- the part of the eye that detects and sends images to the brain -- was linked to attacks by oxidants. Recent evidence suggests that dietary anti-oxidants can help prevent or reduce damage to retinal cells. As a result, Talalay had wondered if sulforaphane might have similar benefits.

In the scientists' experiments, three different cell types were tested, including cancer cells and cells from the retina. When the cells were treated briefly with sulforaphane before exposure to an oxidant, all cell types defended themselves against damage. The extent of protection was tied to the amount of sulforaphane as well as the type of oxidant and its amount.

"This adds to already good evidence that eating large quantities of vegetables -- and cruciferous ones play a special role -- is one thing that really works to fight disease," says Talalay.

First isolated from broccoli, sulforaphane is especially concentrated in three-day-old broccoli sprouts and belongs to a class of molecules called isothiocyanates. Talalay, his colleagues and Johns Hopkins hold patents related to the sulforaphane and broccoli sprout research. In 1998, Talalay, in cooperation with Johns Hopkins University, formed Brassica Protection Products LLC, a Baltimore firm that commissions the growth, harvest and marketing of broccoli sprouts with tested and guaranteed levels of sulforaphane. The terms of this arrangement are being managed by the University in accordance with its conflict of interest policies.
Co-authors on the report are research associates Xiangqun Gao, Ph.D., and Albena Dinkova-Kostova, Ph.D., of the Lewis B. and Dorothy Cullman Cancer Chemoprotection Center and department of pharmacology and molecular sciences at Johns Hopkins.

On the Web:

2001 announcement of how phase 2 enzymes protect against cancer:

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