Plant-Based Fat Inhibits Cancer-Cell Growth By Enhancing Cell's Signaling System, UB Researchers Show

October 25, 1998

BUFFALO, N.Y. -- Nutrition researchers at the University at Buffalo have provided the first evidence that a minor plant-based fat called B-sitosterol appears to play a role in inhibiting the growth of human prostate-cancer cells.

They found that the phytosterol B-sitosterol, a fat abundant in vegetarian diets, enhances an intracellular signaling system that tells cells not to divide. The study showed a 28 percent inhibition of prostate-cancer cell growth after being exposed to B-sitosterol for five days in vitro.

Atif Awad, Ph.D., head of UB's Nutrition Program, will present the results on Oct. 25 at the Sixth International Conference of Anti-Cancer Research in Kallithea, Greece.

"This phytosterol replaces some of the cell membrane's cholesterol, which changes the membrane lipid composition in such a way that signal transduction (secondary messenger activity) is stimulated, and that activation inhibits cell growth," Awad explained.

"If cell proliferation can be stopped before it becomes uncontrolled, cancer can be contained. When we treated prostate-cancer cells with phytosterols, cell proliferation was inhibited. We have found the same effect in vitro with breast and colon-cancer cells."

This activity may help to explain why vegetable fats, such as olive oil, in the diet reduce the risk of developing certain cancers, Awad said.

The work of Awad and colleagues is grounded in epidemiologic studies showing that prostate cancer is less common in Asian countries where diets are primarily vegetarian, and that rates increase when these people migrate to western societies where rates are higher and diets are primarily animal-based.

Working with sterols, a group of minor lipids, Awad and colleagues set out to examine the action of the main plant sterol -- B-sitosterol -- and the main animal sterol -- cholesterol -- on prostate-cancer cell growth.

In previous work, they identified activation of a cell-signaling pathway called the sphingomyelin cycle as one of the inhibitors of cell growth. The UB researchers felt that increased levels of B-sitosterol may amplify the signaling capability of two enzymes that act as second messengers in the sphingomyelin cycle, thus increasing its inhibitory action.

To test their theory, the researchers supplemented human prostate-cancer cell tissue in vitro with either cholesterol or B-sitosterol and monitored cell growth. They also measured activity of the secondary messenger enzymes.

Results showed there were 28 percent fewer cancer cells after five days of B-sitosterol treatment, compared to tissue cultures supplemented with cholesterol.

This inhibition of cell proliferation was accompanied by a 50 percent increase in the activity of one enzyme. The second enzyme showed a 31 percent increase in activity after one day of treatment; an increase of 11 percent remained after five days.

"If we know how phytosterols work, we can advise people how to modify their diets to reduce their risk of prostate cancer, or we could eventually design drugs to target this system," he said

Phytosterols are used widely in Europe to treat enlarged prostate (benign prostatic 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.

Also contributing to the research were Yongmei Gan, a graduate student in nutrition, and Carol S. Fink Ph.D., UB clinical assistant professor of nutrition. The study was supported by a grant from the Allen Foundation.

University at Buffalo

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