How Common Foods Can Specifically Target, Strengthen the Body's First Lines of Defense Against Cancer

American Institute for Cancer Research
Tuesday, 17 July 2001

As Science on the Diet-Cancer Link Progresses, Foods are Showing the Ability to Fight Cancer in Unexpected Ways

Evidence that healthy diets are linked to lower cancer risk has been building for years, but new research is suggesting that certain foods can dramatically bolster the body's primary defenses in several precisely targeted - and unexpected - ways.

Scientists speaking at the 11th Annual Research Conference of the American Institute for Cancer Research (AICR) revealed new evidence showing that substances within herbs, tea, broccoli and other common foods "zero in on" the body's front lines in the war against cancer - the so-called Phase I and Phase II enzymes, which help the body eliminate carcinogens. (For a general background on how this system works, see The Phase I - Phase II System: A Delicate Balance.)

The researchers also presented new evidence that substances in broccoli and broccoli sprouts that have been understood to fight cancer by one method also function in additional, unforeseen ways to bolster the body's cells against the disease. By acting as indirect antioxidants, these substances increase the overall antioxidant capacity of cells, and do so in a varied, long-lasting and safe manner, without exhibiting the potentially dangerous pro-oxidant behavior that can occur with direct antioxidants like vitamins C, E and beta-carotene.

Quattrochi and Wargovich - Phase I Enzymes

When any carcinogen enters the body, it must often be activated by Phase I enzymes. A widely cited example of this system involves hydrocarbons, which can enter the body via charred meat. Under normal circumstances, hydrocarbons bind to a specific receptor that causes Phase I enzymes to be "switched on." Once switched on, the Phase I enzymes go to work transforming hydrocarbons into larger, more reactive (more water soluble) carcinogenic compounds that are easier for the body to dispose of. Occasionally, however, Phase I enzymes generate products that are considerably toxic and carcinogenic themselves.

But it has been shown that when certain dietary components are present - such as certain flavonoids found in tea - these substances bind to precisely the same receptor that hydrocarbons do. As a result, the flavonoid compounds change the way the enzymes are put together so dramatically that the enzymes cannot do their job. When this happens, fewer carcinogens are produced.

Dr. Linda Quattrochi and her colleagues at the University of Colorado Health Sciences Center reasoned that, if one kind of flavonoid binds with one kind of receptor, other flavonoids are likely to bind with other receptors to inhibit Phase I enzymes and other "cancer-promoting" systems. She has found that many different flavonoids found in such foods as oranges, horseradish, mustard, turmeric and both green and chamomile teas can inhibit a wide variety of cancer-promoting reactions.

"These substances seem able to "short-circuit" the cancer process in several different kinds of tissue," she said, "which suggests that flavonoids may be protective against cancer at many different sites in the body."

Dr. Michael J. Wargovich of the South Carolina Cancer Center presented data on the use of natural herbs for cancer prevention. He outlined the important questions regarding safety and efficacy that are now under investigation, and offered caveats regarding the use of herbs in concert with pharmaceutical medications. One example Dr. Wargovich used to illustrate the complex nature of potential herbal-pharmaceutical interactions involved St. John's Wort and its surprising effect on Phase I enzymes.

"About 50% of medicinal drugs utilize the Phase I family of enzymes to get metabolized by the body," Dr. Wargovich said. "But past research has shown that St. Johns Wort activates these very same enzymes."

Thus, when St. Johns Wort is present in the body alongside medicinal drugs used in cancer therapy - such as indinavir, cyclosporin and cyclophosphamide - the cancer drugs become much less effective. Wargovich went on to stress that future research may reveal other herbs that function alongside pharmaceuticals without interfering with them - and perhaps even increase their effectiveness.

He concluded his talk by suggesting that, since the use of anti-inflammatory drugs like aspirin has been associated with risk for several cancers, research now underway may soon show that natural anti-inflammatory compounds in herbs such as feverfew, rosemary and turmeric may also display this same effect on cancer risk.

Talalay's Groundbreaking Work on Phase II Enzyme Inducers

Almost a decade ago, Dr. Paul Talalay of Johns Hopkins University successfully isolated sulforaphane, a natural compound that arises when broccoli (and other cruciferous vegetables) is cooked, chopped or chewed. In repeated experiments, sulforaphane has been associated with a potent ability to "turn on" (or induce) the family of Phase II detoxification enzymes, and to do so precisely, without affecting the Phase I enzymes. These efforts placed Talalay in the vanguard of the (then still dawning) field of diet-cancer research. Over the past ten years, Dr. Talalay and his colleagues have continued this vital work, which has revealed a great deal about the nature of the sulforaphane-Phase II connection. Talalay has shown that different species of broccoli - and even different heads of broccoli - vary greatly in their ability to "turn on" Phase II enzymes. He has also found that a given broccoli plant's inducer potential is related to its genetics, the methods under which it was grown, time and temperature of storage, and means of preparation.

Most recently, Talalay has found that very young broccoli plants - 3-day old broccoli sprouts - are associated with a much higher degree and consistency of boosting Phase II enzyme activity than mature broccoli heads.

Long-Awaited "Proof of Principle"

At the AICR Conference, Dr. Talalay announced two findings that represent significant advances in scientific understanding of the diet-cancer connection.

Dr. Talalay and his colleagues have uncovered direct genetic evidence of Phase II enzymes' central role in cancer protection. Although this long-held hypothesis has been strengthened by repeated laboratory trials over the last ten years, a direct demonstration of the relationship has been lacking. Talalay worked with Masayuki Yamamoto, M.D., Ph.D., of Japan's Tsukuba University and Thomas W. Kensler, Ph.D. of Johns Hopkins University on experiments using "knockout mice" - mice from which a specific gene has been removed. In these experiments, normal mice were exposed to a carcinogen alongside mice that lacked the gene allowing them to "turn on" Phase II enzymes.

Those mice without the Phase II-inducer gene were shown to be more susceptible to tumors. It was also impossible to induce protective Phase II enzymes in these mice, and thus reduce their cancer burden.

"This is an important, long-awaited proof of principle," said Talalay.

New Anti-Cancer Ability Uncovered that is Uniquely Potent, Versatile and Safe

Talalay also announced research showing that the family of compounds known as isothiocyanates (including broccoli's much-studied sulforaphane) shows a surprising ability to fight cancer in an heretofore unforeseen way.

"A broader view of the functional importance of Phase II enzyme inducers like sulforaphane is emerging," he said. "They display a unique and long-lasting chemical versatility. These compounds act in lots of different ways to protect us from cancer, which is very lucky for us indeed."

Apart from their action as potent Phase II enzymes inducers, these compounds seem able to use an entirely different anti-cancer mechanism that has gotten little attention, Talalay said. New evidence indicates that these substances also function as indirect antioxidants.

The distinction between the actions of direct antioxidants and indirect antioxidants is key, Talalay said. Direct antioxidants like vitamin C, vitamin E and beta-carotene wage a one-on-one war against potentially dangerous substances known as "free radicals," which arise as a by-product of normal metabolism. Direct antioxidants bind directly to free radicals before these compounds can inflict the kind of genetic damage that leads to cancer. But several studies have also suggested that direct antioxidants may pose their own risks. Clinical trials involving vitamin C, vitamin E and beta-carotene and other direct antioxidants have shown that, under certain circumstances, these substances may actually inflict genetic damage and increase cancer risk.

Indirect antioxidants cannot and do not bind directly to free radicals. Instead, they use a variety of means to boost the overall antioxidant capacity of cells.

According to Talalay's research, sulforaphane acts as an indirect antioxidant by "turning on" a wide variety of Phase II enzymes that serve to protect the cell from genetic damage. Because sulforphane is capable of inducing so many different Phase II enzymes, which in turn defend against many different kinds of damage, it affords the cell a more varied and efficient form of protection than can be provided by single, direct antioxidants.

Talalay has also found that the overall protection provided by sulforaphane and other Phase II inducers persists for a longer time. Perhaps most importantly, Talalay said, because the overall antioxidant protection afforded by Phase II inducers is indirect, they are unlikely to enter directly into oxidative reactions and exhibit "pro-oxidant" behavior. Thus, sulforaphane is highly unlikely to pose the potential risks associated with vitamin C, vitamin E and other direct antioxidants.

"We now have evidence that the anti-cancer potential of components in cruciferous vegetables like broccoli - and particularly in broccoli sprouts - is longer lasting, more potent, more versatile, and ultimately more safe than we ever suspected," he said.

Dr. Talalay is now at work on clinical trials that seek to determine how to cultivate, prepare and administer broccoli sprout extracts and other plant foods for optimum defense against cancer and other diseases.

For more information, or to contact American Institute for Cancer Research, see their website at: www.aicr.org