Prostate cancer is the most frequently diagnosed malignancy and the second leading cause of cancer deaths in American men today. The discrepancy of prostate cancer incidence between males in Western societies and males in Asian countries correlates to the different dietary styles. We hypothesize that dietary animal and plant sterols may play critical roles in prostate cancer formation/progression, or prevention, respectively. To explore the possibility that cholesterol, the animal sterol, may promote, whereas plant sterols inhibit, prostate cancer formation and progression, we treated human prostate cancer cell lines (PC-3, DU145, LNCaP and C4-2B) with cholesterol or β-sitosterol (β-SIT), the major dietary plant sterol, and analyze the effects of dietary sterols on several parameters of tumor cells related to malignant progression, including proliferation, adhesion, migration and invasion. We found that in general cholesterol promoted prostate cancer cell proliferation, adhesion, migration and invasion ability. In contrast, β-sitosterol suppressed prostate cancer cell proliferation, migration and invasion, but had no or minor effects on adhesion (except for DU145). Specifically, cholesterol significantly promoted proliferation of prostate cancer cell line PC-3 (50.0% increase by comparing with the untreated control group), DU145 (62.5% increase), and LNCaP (31.1% increase), but only a minor promotion on C4-2B (4.2%); whereas β-sitosterol effectively suppressed proliferation of PC-3 (38.3% decrease by comparing with the untreated control group), DU145 (36.3% decrease), LNCaP (33.3% decrease) and C4-2B (60.0% decrease). In addition, by an in vitro invasion assay measuring cell penetration ability through matrigel, cholesterol promoted cell invasion ability of PC-3 (24.6% increase), DU145 (9.8% increase), LNCaP (58.8% increase) and C4-2B (37.0% increase); whereas β-sitosterol suppressed cell invasion ability of PC-3 (28.7% decrease), DU145 (86.8% decrease), LNCaP (41.2% decrease) and C4-2B (17.7% decrease). The potential mechanisms of how dietary sterols mediate promotion or inhibition of prostate cancer progression are also explored. These results suggest that consumption of plant sterol, a naturally present dietary nutrition, and reduction of cholesterol intake, will effectively prevent or retard prostate cancer formation and progression.

This research project was supported by Cancer Research and Prevention Foundation grant and in part by NIH grant (DK65962).

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA