Taking a Closer Look at Phytochemicals

Concepts in Cancer Research

If you saw the following items listed as ingredients on a cereal box, you might be alarmed: isoflavones, terpenes, indoles, phenolic acids. But these tongue-twisters aren't artificial additives, they're naturally occurring chemicals found in fruits, vegetables, beans and whole grains-biologically active chemicals our bodies may use as part of their disease-fighting arsenal. These substances are called phytochemicals (phyto is Greek for plant). Some phytochemicals found in plants not commonly used for food, such as digitalis and quinine, have been used for medicinal purposes for centuries. The anticancer effects of many of them, however, are only beginning to be explored.

Phytochemicals in foods may offer frontline defenses against cancer.

The role of phytochemicals in metabolism has not been adequately defined. A single tomato or orange contains hundreds, and possibly thousands, of phytochemicals. Some are antioxidants, protecting against harmful cell damage from oxidation. Others perform different functions that can help to prevent cancer. Scientists are still deciphering the many ways phytochemicals in foods may offer frontline defenses against cancer.

Phytochemicals as Cancer Preventives

One reason scientists are so excited about phytochemicals is their apparent ability to stop the conversion of a cell from healthy to cancerous at so many different stages. Isothiocyanates, found in cruciferous vegetables (such as broccoli, cauliflower, cabbage and kale) switch on enzymes that actually detoxify carcinogens at an early stage; they also increase the antioxidant defenses of cells. Diallyl sulfides in garlic and onions can stop the growth of cancer cells at a later stage. Saponins, found in beans and other legumes, may prevent cancer cells from multiplying by influencing genetic material in the cells. Ellagic acid, a type of phenolic acid found in strawberries and raspberries, reduces the genetic damage caused by carcinogens in tobacco smoke and air pollutants.

One phytochemical that has received a lot of media attention is lycopene, a member of the vast carotenoid family, which contains more than 600 compounds (including the well-known beta-carotene, as well as lutein and zeaxanthin, which are found in leafy greens). Lycopene, the substance that makes tomatoes red, is being examined because of its possible effects in helping to prevent several types of cancer, including prostate cancer.

The phytochemical properties of soy foods are another hot media topic these days. For many years, research has suggested that soy may be an effective cancer fighter because of the presence of phytochemicals called isoflavones, which may inhibit cancer cell growth and division under some conditions. Cancer researchers began studying soy in an effort to explain why women in Asian countries had far fewer cases of breast cancer than American women; they suggested that soy isoflavones are partially responsible. However, some recent studies have signaled that isoflavones might also produce some negative effects. Dr. Mark Messina, a prominent soy foods expert at Loma Linda University in California, emphasizes that soy is only one of many different plant foods that appear to be effective cancer fighters, and that loading up on any one food is not advisable. Instead, he recommends that, "A balanced diet that includes soy is a good idea, as long as it also includes plenty of vegetables, fruits, whole grains and beans." Soy supplements, however, may contain "mega-doses" of isoflavones, and insufficient evidence has been done so far to verify their safety.

Supported by grants from the American Institute for Cancer Research (AICR), scientists have furthered the research on phytochemicals. Recent studies have investigated how carnosol (found in rosemary) fights breast cancer tumors in laboratory rats, whether curcumin (found in turmeric, a spice) is effective against skin cancer, and the way a substance in green tea (known by the abbreviation EGCG) affects the cell.

Resveratrol, a type of polyphenol found in the skin of grapes and in wine, is currently being widely studied as a cancer preventive agent. It has been found to inhibit human cancer cell growth in the breast, blood and lung as well as blocking tumor growth in rodents. Dr. Zigang Dong from the University of Minnesota has shown that resveratrol inhibits tumor formation in mouse skin cells. In a study currently funded by AICR at the Henry Ford Health System in Michigan, Dr. Subhash Gautum is examining how resveratrol inhibits human leukemia cell growth and whether it can be used to destroy leukemia cells in bone marrow transplants.

Phytochemicals in Cancer Treatment

Some scientists are now studying the use of phytochemicals in cancer treatments, where they are used in such large amounts that they are classified as drugs. This initially involves identifying the active cancer fighting substances in whole fruits or vegetables and then purifying the effective compound. Dr. Peter Ferguson at the London Regional Cancer Center is trying to determine the phytochemicals in cranberry products that may inhibit the growth of breast cancer cells and slow metastasis. Just like other chemicals, however, phytochemicals may be toxic in large amounts and must be properly formulated and tested before using.

Choose Whole Foods

Although there's still much that is unknown about phytochemicals, what scientists do know from many human population studies worldwide is that people who eat large quantities of fruits and vegetables have reduced cancer risks.

What about supplements? Phytochemicals are already appearing in pills, potions, powders and drinks, but experts believe that it is more effective to get cancer-protective substances by eating whole foods-vegetables, fruits, whole grains and beans. "A good example of how we learned this was with beta-carotene," says Stephen Barnes, Ph.D., a pharmacology professor at the University of Alabama at Birmingham.

"All the evidence showed that foods rich in beta-carotene were beneficial, but when we tested the chemical by itself [in supplement form] it was not effective in preventing cancer." Two beta-carotene studies showed that smokers taking the supplement developed more cases of lung cancer. It could be the same story with other phytochemicals. "It may be that these compounds are highly interactive and do not work well when they're isolated," says Barnes. Most of these compounds, however, have yet to be tested as part of a mixture.

Research started by the National Cancer Institute (NCI) to study the effects of various phytochemicals was dubbed the Designer Foods Research Project when it was first announced in 1989 by Ritva Butrum, Ph.D., then Chief of NCI's Diet and Cancer Branch and now Vice President for Research at AICR. Carolyn Clifford, Ph.D., who directs the program today, says the technology is far ahead of the science at this point. "You can modify the chemical constituents in food through plant breeding, bioengineering and food processing, but before we get to the next stage we need to know: What compounds? What levels are effective?" says Clifford.

People who eat large quantities of fruits and vegetables have reduced cancer risks.

In other words, would megadoses of certain phytochemicals really head off cancer? Could they have harmful side effects? Does the preventive punch of phytochemicals depend upon dozens or hundreds of them working together, as they exist naturally in foods?

Dr. Messina does not endorse the trend toward souped-up cereals, fortified snack foods or what might be called "phytamin" pills. "I think we should focus our time on getting people to consume the type of diet we already know will reduce cancer risk. The notion of 'designer foods' is in essence trying to supplement your way to good health. It doesn't make up for a bad diet," he says.

The Take-Home Message

Although soy foods, cruciferous vegetables and citrus fruits are developing reputations as phytochemical powerhouses, these are only the most studied foods to date. Scientists are learning more about phytochemicals that exist in all plant-based foods every day. Eating a wide variety of vegetables, fruits, whole grains and beans is more important than concentrating on particular foods, in order to get the full gamut of phytochemicals found in nature.

Here are some easy ways of increasing your intake of phytochemicals:

• Eat a variety of vegetables. Broccoli is very nutritious, but you don't have to eat it every day. Also try carrots, cauliflower, leafy greens, winter and summer squashes, green and red peppers, onions, snow peas, red cabbage…the list is endless. Don't feel you have to eat a wide variety every day; your weekly consumption is what's important. Aim for at least three servings of vegetables a day.
• Eat more fruits. A glass of juice at breakfast is nice, but how about some peaches, blueberries or bananas atop your cold or hot whole-grain cereal? A fruit salad with lunch or a juicy orange as midday snack? A bowl of perfectly ripe strawberries after dinner? Branch out and have cherries, figs, melon, kiwi, plums, mango, pineapple or grapes. Aim for at least two servings of fruits per day.
• Eat more whole grains. Don't limit your choices to bread, rice and pasta. Try quinoa, bulgar, barley and kasha for variety. Once available only in health food stores, most of these foods have become supermarket staples. Eat more beans. Think kidney beans, chickpeas, white beans, navy beans, pintos and dried legumes like lentils and split peas. Many are available canned, so you don't have to cook them from scratch-just rinse under water to get rid of extra sodium.
• Don't forget herbs and spices. Even though you don't eat much of them, they contain phytochemicals too. Garlic, oregano, basil, parsley, orange peel, ginger and other fresh and dried herbs and spices add zip to lowfat foods.
• Decrease portion sizes of meat, fish and poultry. You'll naturally eat more vegetables, beans and grains if you do. Remove half the meat filling from an overstuffed deli sandwich and pile on the veggies. Add more beans and less beef to your chili. Make a stir-fry with more vegetables and brown rice and less chicken.
• Explore new foods and new recipes. Tofu may be a phytochemical-filled option, but knowing how to prepare it may be a challenge. The same may be true for unfamiliar offerings in the produce department, like jicama, fennel, tomatillos, daikon, papaya or passion fruit. Some supermarkets offer recipe cards or fliers to encourage customers to try more exotic fare. Or pick up a lowfat or vegetarian cookbook for tips.

AICR Research Grants on Phytochemicals

The American Institute for Cancer Research (AICR) has taken a leadership role in supporting research in the area of phytochemicals, nutrition and cancer. Following is a partial list of grants awarded by AICR in this area.

Effect of Soy Isoflavone Consumption on Plasma Hormones Related to Prostate Cancer Risk in Healthy Young Men
Alison Duncan, Ph.D.
University of Guelph
Guelph, Ontario, Canada

Inactivation of CYP1A1 by Flavones - Lung Cancer Prevention
Thomas Walle, Ph.D.
Medical University of South Carolina
Charleston, South Carolina

Determination of Cranberry Constituents with Antiproliferative Activity Against Human Tumor Cell Lines
Peter Ferguson, Ph.D.
London Regional Cancer Center
London, Ontario, Canada

Preclinical Evaluation of the Anti-leukemia Effects of Plant-derived Monoterpenes
Steven Clark, Ph.D.
University of Wisconsin
Madison, Wisconsin

Mechanisms of Flavonoids as Chemoprotective Agents
Thomas Gasiewitz, Ph.D.
University of Rochester
Rochester, New York

Antitumor Effects of Dietary Isothiocyanates on Prostate Cancer
Tse Hua Tan, Ph.D.
Baylor College of Medicine
Houston, Texas

Editorial Review Committee
Ritva Butrum, Ph.D.; Karen Collins, M.S., R.D.; Elaine Feldman, M.D.; David Heber, M.D., Ph.D.; Jan Kasofsky, Ph.D., R.D.; Laurence Kolonel, M.D., Ph.D.; Helen Norman, Ph.D.; Melanie Polk, M.M.Sc., R.D., FADA; th American Institute for Cancer Research Executive Staff.

References

1. Eat to Heal, Kristine M. Napier, Warner Books, Inc., 1998.
2. Food, Nutrition and the Prevention of Cancer: a global perspective, World Cancer Research Fund/American Institute for Cancer Research, 1997. Chapter 5.8 "Other Bioactive Compounds."
3. Functional Foods & Nutraceuticals in Cancer Prevention, Ronald R. Watson, ed., Iowa Press, 2003.
4. Natural Compounds in Cancer Therapy, John Boik, Oregon Medical Press, 2001.
5. Interviews with: Stephen Barnes, Ph.D., University of Alabama at Birmingham; and Mark Messina, Ph.D., Port Townsend, WA.

The information in this publication is intended for educational purposes only. No endorsement is being made of any institution, individual, product or program.

E3C-TLP/E79

2002 American Institute for Cancer Research

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