Uncorking a wine-related cancer treatment
January 22, 2009

MADISON — Resveratrol – that intriguing substance that seems to make red wine heart-healthy – is being proposed for clinical trials later this year against neuroblastoma, a type of cancer that affects infants and young children, says Dr. Arthur Polans, professor of ophthalmology and visual sciences at the University of Wisconsin School of Medicine and Public Health.

Polans’ laboratory, part of the UW Paul P. Carbone Comprehensive Cancer Center, has been studying the substance for about five years, and has been using it successfully to treat several types of cancer in mice. His research group has applied for permission to use it to treat neuroblastoma, a nervous-system cancer that mostly affects babies and children.

“Resveratrol is a promising treatment for young children because it’s not toxic to healthy cells, only to cancer cells,’’ Polans said. “How do you treat infants without causing other problems in the years to come? That is the kind of question that intrigues us.”

Because it seems to kill cancer kills while leaving healthy tissue alone, resveratrol is also being looked at to treat ocular or uveal melanoma, a cancer of the eye that can lie dormant for many years before metastasizing and becoming fatal. So far, there are no good treatments for melanoma that begins in the colored tissues of the eye; it doesn’t respond the same way as melanoma that begins in the skin.

“It’s one of those rotten cancers,’’ Polans said. “We don’t know what causes it and we don’t know how to treat it effectively.”

While the cancers are very different, adults who develop melanoma of the eye have something in common with babies who develop neuroblastoma – they may live for a long time after their diagnosis, so potential treatments shouldn’t cause other health problems.

 “What neuroblastoma and uveal melanoma have in common is the factor of time,” said Polans. “Ideally, you’d like to be able to treat them aggressively at first, and then treat them with lower doses of a non-toxic compound over time.  Otherwise, you run the risk of damage to vital organs or an increase in secondary tumors.”

So far, the Polans lab has shown that resveratrol shrinks tumors and kills malignant cells in five types of cancer: skin melanoma, breast cancer, neuroblastoma, ocular melanoma and retinoblastoma. A poster outside Polans’ office shows a mouse with a large neuroblastoma tumor that is then shrunken to nothing by resveratrol.

“Mice that were treated with resveratrol are healthy, gain weight and don’t seem to have side effects,’’ he said, “but when you look at the cancer cells, they’re dying.”

Polans’ lab has also done a lot of basic research on resveratrol, developing new forms of the compound that are more potent, and active in the body for longer than the common forms of the substance.

If it proves its worth, resveratrol will join a large class of cancer-fighting compounds derived from plants, including taxol, which comes from yew trees, and etopside, derived from the mayapple. Resveratrol, which can be derived from grape skins, is also seen as the substance at work in the so-called  “French Paradox,’’ in which French hearts stay  healthy (thanks to drinking red wine) despite all that brie cheese and liver paté.

“About 70 percent of new chemotherapeutics are derived from natural products or based on their structures,’’ says Polans. “There’s a lot of interest worldwide in finding new substances from plants and other natural sources, including microbes from the soil and a variety of species from the ocean.”