COLUMBUS, Ohio -- A low-calorie diet slows the progress of prostate cancer in animals, new research shows.
The slowing of tumor progression occurred whether the calories were reduced by cutting fat, carbohydrates, or the overall diet.
The results further suggested the way that the lower-calorie diet slowed tumor growth in rats and mice -- it retarded 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, director of cancer prevention and control at the Ohio State University Comprehensive Cancer Center—Arthur G. James Cancer Hospital and Richard J. 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 studies of the relationship between diet and prostate cancer in humans.
The paper by Clinton and a team of researchers appeared in the March 15 issue of the Journal of the National Cancer Institute. It 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. One group of rats was allowed to eat as much as desired. Castrated rats made up a second group that was also allowed to eat freely. The third and fourth groups were fed diets containing 20 percent and 40 percent fewer calories, respectively, than the groups with restricted diets.
The researchers used castrated rats because depriving prostate tumors of male hormones, androgens, is one of the most effective ways of slowing prostate tumor growth. Clinton wanted to know how diet would affect tumor growth compared to the gold standard of androgen deprivation.
The second experiment also involved groups of castrated and non-castrated rats that were allowed to eat at will, plus three other groups fed 30 percent 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, weighed, and measured the tumors. They also examined tumor structure, rates of cell proliferation and cell death, and numbers of blood vessels within each tumor.
Last, they measured the activity of the gene for vascular endothelial growth factor (VEGF), a substance produced by tumor cells that stimulates blood vessel growth.
In the third set of experiments, the researchers transplanted human prostate-tumor cells into mice lacking an immune system (i.e., severe combined immunodeficient [SCID] mice). This approach allowed the investigators to determine if human prostate cancer cells might also be sensitive to the 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 percent fewer calories. As in the preceding rat experiment, one group received total dietary restriction, while the second and third groups were restricted by fat and carbohydrates.
All experiments ran for 16 weeks. Non-castrated rats from the first experiment had tumor diameters averaging 2.2 cm. Castrated rats, on the other hand, had tumor diameters only about one-fourth that size on average.
Animals fed 40 percent fewer calories had tumors averaging about 60 percent the size of castrated rats, while those fed 20 percent fewer had tumors that were three-quarters the size of those in castrated animals.
The second rat experiment showed 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 where 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 Clinton.
The study also suggested that both castration and a low- calorie diet reduced angiogenesis -- the growth of new blood vessels -- in prostate tumors, and the production of growth factors by tumor cells 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 Clinton.
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