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Grapes provide some of the natural agents studied in the prevention of skin cancer in mice at the UT Health Science Center San Antonio. Photo courtesy of the USDA Agricultural Research Service/Peggy Greb
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SAN ANTONIO (Aug. 26, 2010) — Maybe you worshipped the sun in your youth or weren’t as meticulous as you should have been with sunscreen. If so, take heart: Scientists at The University of Texas Health Science Center San Antonio are finding that certain plant substances, when given in combinations, may suppress damage that can cause skin cancer.

The substances, which occur naturally in grapes, berries, walnuts and a number of other plant-based foods, were tested on mice that had been genetically manipulated to be sensitive to skin cancer initiation and its promotion and progression. Given in combination, even at low doses, the plant agents proved protective.

“On the basis of our research, supplements and creams or sunscreens may be developed, tested in humans and then used to prevent skin cancer,” said Zbigniew Walaszek, Ph.D., research associate professor of pharmacology at the Health Science Center.

The natural agents include resveratrol, found in the skin of red grapes, and grape seed extract. Others are calcium D-glucarate, a salt of D-glucaric acid, which is present in the human bloodstream and in many fruits and vegetables, and ellagic acid, found in a host of berries and in walnuts.

Synergistic effects
Each of these compounds works in a different way, so giving them in combinations is most protective. Scientists have administered the agents both topically and in the diet.

In one study, the team induced skin cancer by shaving the backs of rodents and applying a chemical that produces a genetic mutation. This was done twice a week for four weeks. At the same time, researchers applied topical resveratrol and fed the mice diets supplemented with various combinations of the plant substances.

The team evaluated several outcomes, including thickness in the outer layer of the skin. An increase in thickness indicates that precancerous cells are multiplying. Researchers also monitored mutations in Ha-ras, an oncogene that is a biomarker of cancer initiation, and inflammation, which is important in tumor promotion.

Even low doses of the plant agent combinations produced protective effects, while the plant substances given individually produced markedly less benefit.

This drawing shows the layers of skin and associated glands and vessels, including the epidermis, dermis, fatty tissue, blood vessels, follicle, oil gland and sweat gland. Illustration courtesy of the National Cancer Institute/Don Bliss

Preventing cell transformation
Dr. Walaszek’s colleague and wife, Margaret Hanausek, Ph.D., research associate professor of pharmacology, said the findings hold great potential for those most at risk for skin cancer and other cancers involving epithelial cells, including lung cancer.

“The combined inhibitory effects of different plant chemicals are expected to be particularly beneficial to, for example, smokers, former smokers or individuals with heavily tanned skin, who carry thousands of cells already initiated for malignant transformation,” Dr. Hanausek said.

Research scientist Magdalena Kowalczyk, Ph.D., agreed: “Described combinations may be very useful in the prevention of skin cancer and other epithelial cancers in humans, achieving a high efficacy and potency with reduced side effects.”

The team continues to look for the best combinations of the natural agents in suppressing different events during skin cancer development, she said.

Future directions
Researchers acknowledge that not all information — for example, effects on organs such as the lungs — can be gleaned from a skin cancer model. But they say it is an exciting start.

“The team’s next step is to go to an ultraviolet B light model of skin cancer initiation and confirm the results,” Dr. Walaszek said.

Team leader Thomas Slaga, Ph.D., professor of pharmacology at the Health Science Center, developed the mouse model of skin cancer. Called SENCAR, it is used by scientists worldwide.

The ongoing work is supported by two grants from the National Institutes of Health.

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The University of Texas Health Science Center at San Antonio, one of the country’s leading health sciences universities, ranks in the top 3 percent of all institutions worldwide receiving National Institutes of Health (NIH) funding. Research and other sponsored program activity totaled a record $259 million in fiscal year 2009. The university’s schools of medicine, nursing, dentistry, health professions and graduate biomedical sciences have produced approximately 26,000 graduates. The $739 million operating budget supports eight campuses in San Antonio, Laredo, Harlingen and Edinburg. For more information on the many ways “We make lives better®,” visit www.uthscsa.edu.