NIH Scientists Discover How Restricted Diets Slow Cancer; Advance Suggests a Drug Might Be Developed to Do the Same

Scientists at the National Institute of Environmental Health Sciences today announced they've discovered how calorie-restricted diets can slow the development of at least one major cancer -- a discovery that they hope will lead to a drug, or other measure, with the same cancer-retarding effect.

For many years, studies have shown that animals on calorie-restricted diets have less cancer and fewer signs of aging. Today, NIEHS scientists Sandra Dunn, Ph.D., Frank Kari, Ph.D., Jeff French, Ph.D., and Scientific Director and Molecular Laboratory Chief J. Carl Barrett, Ph.D., along with other colleagues, reported in the journal Cancer Research that diet restriction delays tumor progression by reducing a hormone in the blood and body called insulin-like growth factor 1. IGF-1 is related to human growth hormone, which spurs the growth of the body's long bones, and thus height.

The scientists said that they have demonstrated in mice with bladder cancer that cancer's uncontrolled growth and malignant properties appear to be stimulated by IGF-1 and that a diet-caused reduction in IGF-1 reduces the cancer cells' proliferation and stimulates the death of the cancerous cells. In doing so, it retards the spread and growth of established cancers.

Members of this research group had previously shown that dietary restriction reduced circulating levels of IGF-1 and significantly reduced the development of spontaneous cancers in the first place.* In the new work, the growth of established cancers was greatly reduced and then increased by reducing or adding IGF-1:

Mice were given a chemical, p-cresidine, to induce bladder cancers very similar to human bladder cancers. Subsequently, when the calorie content of the mice diet was restricted 20 percent, insulin-like growth factor-1 declined 24 percent and the bladder cancer's progression and spread decreased as well.

To be sure IGF-1 was the key, the scientists restored the IGF-1 levels in the diet-restricted animals and saw the bladder cancers increase. Mechanistically, this occurred through both increased cell proliferation (five-fold) and decreased rates of cell death (ten- fold).

Dr. Dunn and colleagues carried out their research in mice genetically modified to be like cancer-prone humans. That is, the mice are modified to be deficient in the gene, p53, the gene found impaired in many cancers.

Although the research involved bladder cancer-which will be diagnosed in an estimated 52,000 Americans this year-the scientists believe their finding applies to cancer generally, just as earlier dietary findings applied to various cancers.

Dr. Dunn said, "Our studies suggest that IGF-1 may be a good target for cancer prevention and possible therapeutic intervention."

Asked if a pill could be devised to reduce IGF-1 and produce a beneficial effect in humans, Dr. Kari said, "Yes, our work identifies a previously unidentified function of a well-studied hormone-so it is not a big leap to envision pharmacological manipulation of its activity in humans."

The scientists said the study also adds to the understanding of how calorie-rich diets contribute to an increased risk of many cancers. Scientists have known for more than 30 years that calorie restrictions can prevent or retard cancers in animals, and also retard aging, but few people have been able to follow such diets, or wanted to.

In fact, despite the known health risks, the percentage of Americans who are overweight has been increasing.

Calorie-reduced diets have also been demonstrated in animals to retard aging but this study did not attempt to show if a reduction in IGF-1 would have the same effect, Dr. Kari said, "although you would expect that a reduction in cancer would also extend life expectancy."

Diet has been estimated to contribute to more than one third of all cancer deaths in the western world.**

Working with Drs. Dunn, Kari, French and Barrett were Gregory S. Travlos, Ph.D., and Ralph E. Wilson.

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*Kari et al, Cancer Research, Vol. 53: 2750-2757, 1993.

**R Doll and R Peto, "The causes of cancer: Quantitative estimates of avoidable risks of cancer in the United States today," Journal of the National Cancer Institute, Vol. 66:1191-1309, 1981.