Dietary
phytosterol supplements are readily available to consumers since they effectively reduce plasma
low-density lipoprotein cholesterol. Several studies on cell cultures and xenograft mouse models suggest that dietary
phytosterols may also exert protective effects against common
cancers. We examined the effects of a dietary
phytosterol supplement on
tumor onset and progression using the well-characterized mouse mammary tumor virus polyoma virus middle
T antigen transgenic mouse model of inherited
breast cancer. Both the development of mammary hyperplastic lesions (at age 4 weeks) and total
tumor burden (at age 13 weeks) were reduced after dietary
phytosterol supplementation in female mice fed a high-fat, high-
cholesterol diet. A blind, detailed histopathologic examination of the mammary glands (at age 8 weeks) also revealed the presence of less-advanced lesions in
phytosterol-fed mice. This protective effect was not observed when the mice were fed a low-fat, low-
cholesterol diet.
Phytosterol supplementation was effective in preventing
lipoprotein oxidation in mice fed the high-fat diet, a property that may explain - at least in part - their anticancer effects since
lipoprotein oxidation/
inflammation has been shown to be critical for
tumor growth. In summary, our study provides preclinical proof of the concept that dietary
phytosterols could prevent the
tumor growth associated with fat-rich diet consumption.