Plant-Based Fats Slow Prostate Cancer Growth in Mice

BUFFALO, N.Y. -- Fats derived from plants appear to inhibit the growth and migration of one type of prostate cancer cell and to slow the growth of prostate tumors in laboratory mice, nutrition researchers at the University at Buffalo have found.

Conversely, those fed a diet supplemented with cholesterol had larger tumors and twice the amount of metastasis in lung and lymph nodes than those receiving the plant-fat diet, results showed.

This is the first report of the effect of plant-derived fats on human prostate-cancer cell growth and metastasis in animals. Results of the study appear in the December 2001 issue of European Journal of Cancer Prevention.

The study was conducted by researchers led by Atif B. Awad, Ph.D., associate professor of nutrition in the Department of Physical Therapy, Exercise and Nutrition Sciences in the UB School of Health Related Professions and director of UB's nutrition program.

The researchers report that prostate-cancer tumors were 40 percent smaller in animals fed a diet enhanced with phytosterols than in animals fed a diet enhanced with cholesterol.

Phytosterols is the general name for plant-based fats, which are found primarily in unfiltered vegetable oils such as virgin olive oil, peanut oil and canola oil.

In cultures of prostate-cancer cells, a specific plant fat called B-sitosterol inhibited the growth of cancer cells by 70 percent compared to controls, results showed. Phytosterols also inhibited the ability of cancer cells to migrate and bind to membrane proteins of normal cells.

"These studies demonstrated for the first time that phytochemicals that exist naturally in our diet can protect against prostate cancer by inhibiting the growth of the human tumor and its spread in the host's tissues, both in animals and the laboratory," Awad said.

The research is aimed at understanding why prostate cancer is the most common male cancer in Western societies, but is significantly less common in Asia. One of the primary differences between the cultures is diet, specifically the amount of vegetable versus animal fat consumed. Western diets are high in cholesterol, but low in phytosterols, while the opposite is true of the typical Asian diet.

Awad and colleagues have been studying the significance of this dietetic difference and the relationship to breast and prostate cancer for several years. In previous pioneering work on human prostate-cancer cells (type LNCaP) they found that B-sitosterol, a fat abundant in vegetarian diets, inhibited tumor growth and reduced the level of PSA released.

They also have shown that plant-based fats appear to cut the risk of prostate cancer by reducing the levels of both testosterone and certain enzymes that metabolize testosterone into more active forms, and that B-sitosterol stimulated cell death in both LNCaP prostate cancer and one type of breast-cancer cells in the laboratory.

Feeding phytosterols to mice injected with breast-cancer cells reduced tumor growth and metastasis, but until now no information was available on the effect of phytosterols on growth and metastasis of human prostate cancer.

Phytosterols are used widely in Europe to treat enlarged prostate (benign prostate hyperplasia), Awad said, and are known to lower the risk of cardiovascular disease by interfering with cholesterol absorption. B-sitosterol is abundant in unrefined vegetable oils, such as virgin olive oil.

To determine the effect of cholesterol and phytosterols on human prostate-cancer cells, Awad and colleagues simulated Western and Asian diets by feeding one group of mice a mix of phytosterols and another group cholesterol with their normal food. After a two-week adaptation period, they introduced PC-3 human prostate-cancer cells into both groups and maintained the mice on their respective diets for eight more weeks.

Concurrently, they conducted cell-culture studies in which PC-3 cells were exposed to three different types of dietary fat: B-sitosterol and campesterol -- both phytosterols -- and cholesterol. A control cell culture contained tumor cells with no supplementation. Cells were grown for three days, then counted and tested for invasiveness, adhesiveness to cell membrane proteins and ability to migrate.

Eight weeks after inoculation, tumors in phytosterol-fed mice were 40-43 percent smaller than tumors in cholesterol-fed mice, researchers found. In addition, phytosterol-fed mice showed half the rate of PC-3 cell metastasis to other organs.

In the cell-culture experiments, the number of cancer cells in the cholesterol-supplemented medium increased by 18 percent over three days, while tumor cells decreased by 70 percent and 14 percent in B-sitosterol and campesterol-supplemented media, respectively, compared to the control.

Phytosterol-treated PC-3 tumor cells were 78 percent less invasive than controls, compared to a 43 percent increase in invasiveness for cholesterol-exposed cells. Cholesterol also increased cell migration by 67 percent, while B-sitosterol and campesterol decreased migration by 93 percent and 60 percent, respectively, compared to controls.

Both phytosterols reduced tumor-cell adhesion to the cell-membrane protein laminin, and B-sitosterol reduced adhesion to the protein fibronectin. Cholesterol increased PC-3 binding to one type of collagen, the primary protein of all connective tissue.

"The findings demonstrate that the consumption of foods rich in phytosterols is beneficial to protect from prostate cancer," Awad said. "The FDA has approved including phytosterols in margarines and other food products, which now are available commercially, to help lower cholesterol in the blood.

Awad said phytosterols can be incorporated easily in the diet by eating phytosterol-rich foods, such as unrefined plant oils, nuts and legumes. They also can be obtained in a pill form from natural food stores, he noted, but dietary sources are better because they may provide other nutrients that also may offer protection from prostate cancer.

Carol S. Fink, Ph.D., and Heinric Williams of the UB Department of Physical Therapy, Exercise and Nutrition Sciences, and Untae Kim, M.D., of the Buffalo VA Medical Center, contributed to this research, which was supported by a grant from the Peanut Institute.