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Vol. LXV, No. 2
January 18, 2013
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Got Ginger?
Dong Speaks on Nutritional Foods, Cancer Prevention

On the front page...

Dr. Zigang Dong
Cancer remains one of the leading causes of death in today’s world, says Dr. Zigang Dong, director of the Mayo Clinic’s Hormel Institute and professor at the University of Minnesota.

He recently visited NIH to give a talk titled “Can We Win the War Against Cancer by Prevention?” This was part of the Stars in Nutrition and Cancer Lecture Series, sponsored by NCI’s Division of Cancer Prevention.

Many kinds of cancer trends—including the incidence of lung and stomach cancer—are going down, he said. And yet in the U.S., the total cancer incidence and death rate has dropped only slightly.

Continued...

Prevention is critical to lowering the worldwide incidence of cancer, still the number 1 cause of death for Americans under 80.

“Cancer and prevention are tightly linked,” Dong told the audience in Lipsett Amphitheater. A leader in research on ultraviolet light-induced skin cancer, he focuses on its molecular mechanisms in mouse models.

“I would like to emphasize that we have a lot of achievement,” he said, “but it’s not good enough compared to scientists in the cardiovascular disease area. They have a very strong prevention program.”

One of Dong’s major goals is to identify agents with low toxicity, fewer side effects, usable alone or with traditional chemotherapeutic agents to prevent or treat cancer.

Why the focus on nutritional foods?

“Cancer and prevention are tightly linked,” Dong told the audience in Bldg. 10’s Lipsett Amphitheater.

“Cancer and prevention are tightly linked,” Dong told the audience in Bldg. 10’s Lipsett Amphitheater.

Photos: Bill Branson

The idea of food as medicine, said Dong, is not a new one. Many dietary factors have potent anticancer activities, but they work through mechanisms that are still unknown.

Cancer is complicated, with a multistage process of initiation, promotion and progression. Preventing it is also complicated. For one thing, a study in prevention can be more difficult than a study in disease, where you can more readily see an effect.

And isolating beneficial plant compounds, called phytochemicals, is tricky. It’s also hard to study them as a mixture: Do you look at substances A and B—or B and C—or the whole thing together?

So is green tea good for you? Its phytochemicals may be biologically meaningful, but they don’t necessarily translate to clinical applications. Yet.

“So please don’t think of this as a lecture,” said Dong, who completed postdoctoral training at NCI-Frederick. “This is just a progress report by an NIH-trained student.”

To appreciate that progress, think of the body as an intricate network of cells in a constant, but stable, state of change.

Then imagine a single cell as a microscopic city-state that produces a lot of industry and commerce within its walls. It also communicates with the domain outside those walls. Its boundaries are dynamic, busy with sending and receiving stations. Some stations are like piers where external molecules from hormones, food or drugs can pull in and dock—blocking other molecules in the process. Or they may be allowed entry into the cell itself.

To do its work, the cell makes its own molecules for signaling, pathway and transduction (the transfer of genetic material). These let the cell read and adapt to events both inside and outside its walls. Such microscopic cellular processes are so complicated that they make our vast human bureaucracies look simple.

And to complete all these tasks, the cell needs work orders. These are found in the genes, which contain DNA, the set of instructions for making proteins (the building blocks of life) as well as RNA (the intermediary). How these instructions develop depends on the specifics and the timing of gene expression.

“This is my dream,” said Dong, “to rewrite the history of nutritional science.”

“This is my dream,” said Dong, “to rewrite the history of nutritional science.”

Expression is a crucial process, because it turns the gene’s instructions into something the body can use, like the proteins that operate our cells.

Genes can also contain mutations implicated in cancer.

Working on this intricate microscopic level, Dong investigates the cell’s response to tumor promoters. These are like docking stations for proteins that control when genes are expressed.

He also studies protein kinases, enzymes that modify other proteins. Protein kinases have profound effects on a cell, as they regulate the majority of cellular pathways.

By focusing on these specific molecular mechanisms, Dong has discovered that several are critical in cancer development.

His lab has also identified key molecular targets for screening novel natural anticancer drugs with fewer side effects. Many of these compounds appear to act on tumor-promoter-stimulated pathways.

Various dietary factors—including those isolated from green and black tea, broccoli, red grapes, ginger root and rice—can have effects on key signaling molecules.

“Our lab focused on green tea and ginger,” Dong said. “When gingerol was painted on mouse skin it was found to be more powerful than the control with a conventional chemotherapeutic agent.” To find the mechanism for how gingerol works, his lab has chosen it for further study.

He has also taken a major step in understanding the mechanisms of anticancer effects of green tea in the mouse model.

Green tea now looks promising, but Dong cautioned that we cannot assume that nutritional compounds are safe. For example, some reports now show that capsaicin, the “hot” ingredient in spicy peppers, may have cancer-causing effects.

More large-scale animal and molecular biology studies are still needed to address the bioavailability, toxicity, molecular targets, pathways and side effects of dietary factors. There are currently two clinical trials in breast cancer prevention at the University of Minnesota.

“This is my dream,” said Dong, “to rewrite the history of nutritional science.”


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