Low-Calorie Diet Slows Prostate Cancer in Animals

New research shows that a low-calorie diet slows the progress of prostate cancer in animals. Tumor progression was inhibited irrespective of how the calories were reduced; ie, by cutting fat or carbohydrates or by changing the overall diet. The research suggested further that the way in which the lower-calorie diet slowed tumor growth in rats and mice also helped retard the development of new blood vessels in the tumor.

“This study clearly demonstrated in two different animal models that energy intake influences the growth of prostate tumors,” said Steven Clinton, md, phd, director of cancer prevention and control at the Ohio State University Comprehensive Cancer Center–Arthur G. James Cancer Hospital and Solove Research Institute. “Our findings provide further evidence that prostate-cancer development might be influenced by lifestyle. They also suggest that maintaining a proper energy balance—an appropriate weight for height—may inhibit the progression of prostate cancer.” In addition, these results will help clinical investigators design other studies to explore the relationship between diet and prostate cancer in humans.

Three Sets of Experiments

The study, which appeared in a recent issue of the Journal of the National Cancer Institute, involved three sets of experiments—two using rats and one using mice.

In the first set of experiments, malignant cells from a form of rat prostate cancer were transplanted into four groups of cancer-free rats. Each group of rats was then assigned a specific diet. One group was allowed to eat as much as desired. A second group, made up of castrated rats, was also allowed to eat freely. The third and fourth groups were fed diets containing 20% and 40% fewer calories, respectively, than the groups following unrestricted diets. The researchers used castrated rats because depriving prostate tumors of androgens is one of the most effective ways of slowing tumor growth. Clinton was investigating how diet would affect tumor growth compared to the standard method of androgen deprivation.

The second experiment also involved groups of castrated and noncastrated rats that were allowed to eat at will, plus three other groups fed 30% fewer calories. The groups differed in the source of caloric restriction. One group

had fewer calories from fat, another had fewer calories from carbohydrates, and a third had fewer calories in the overall diet.

After 16 weeks, the researchers removed the tumors and weighed and measured them. They examined tumor structure, rates of cell proliferation and cell death, and the number of blood vessels within each tumor. They also measured the activity of the gene for vascular endothelial growth factor (VEGF).

In the third set of experiments, the researchers transplanted human prostate tumor cells into mice lacking an immune system (ie, severe combined immunodeficient [SCID] mice). This approach allowed them to determine whether human prostate cancer cells might also be sensitive to dietary intervention. Four groups of mice were used. One group was allowed to eat at will, while the other three were fed diets containing 30% fewer calories. As in the preceding rat experiment, one group was fed a totally restricted diet, while the second and third groups were fed diets restricted in fat and carbohydrates.

Fewer Calories Equals Smaller Tumors

All experiments ran for 16 weeks. Noncastrated rats from the first experiment had tumor diameters averaging 2.2 cm. Castrated rats, on the other hand, had tumor diameters averaging only about one-fourth that size. Animals fed 40% fewer calories had tumors averaging about 60% of the size of tumors in castrated rats, while those fed 20% fewer calories had tumors that were three-quarters of the size of tumors in castrated animals.

The second rat experiment demonstrated that the type of caloric restriction— whether overall, or from fat or carbohydrate—had no significant influence on tumor size. All slowed tumor growth to a similar degree.

The mouse experiment using transplanted human prostate tumor cells also showed that a diet lower in calories slowed prostate tumor growth, regardless of how the calories were cut.

“It may be that a high-fat diet has little influence on prostate cancer if men exercise, consume a diet of modest calories, and maintain a lean body mass and an appropriate weight for their height,” said Dr. Clinton.

Angiogenesis Also Reduced

The study also suggested that both castration and a low-calorie diet reduced angiogenesis in prostate tumors, as well as the production by tumors cells of growth factors that promote angiogenesis.

“We now need to conduct nutritional studies in men with early prostate cancer to learn if dietary changes can alter the course of their disease, and if so, whether it is related in some way to tumor angiogenesis,” said Dr. Clinton.