Effect of β-sitosterol on growth and differentiation of LNCaP human prostate cancer cells

Phytosterols are plant sterols found in soy and other plant products. Populations consuming large amounts of plant products have lower mortality from prostate cancer. The objective of this study was to compare the effect of the animal sterol cholesterol (CL) and the plant sterol β-sitosterol (β-S) on growth and differentiation of the LNCaP cells. Cells were grown in DMEM supplemented with up to 16 μM sterol delivered by a cyclodextrin vehicle. Growth was measured by cell counting on days 1, 3, and 5 of treatment. There was no significant effect on cell growth after one day of treatment. Growth was significantly inhibited by 16 μM β-S compared with 16 μM CL on days 3 and 5. On day 3, growth of cells treated with 16 μM β-S was 72% of cells treated with 16 μM CL when growth was expressed as percent of control. On day 5, this ratio was reduced to 66%. Culture media and cell lysates were assayed for total (ACP) and prostatic acid phosphatase (PAcP), a prostatic epithelium-specific differentiation antigen. No significant differences were observed in ACP or PAcP secreted into the media on days 3 or 5. PAcP in the cell lysate was significantly higher in the 4 μM CL (3.19 U/mg prot) than the 4 μM β-S (2.42 U/mg prot) on day 5. When the concentration of CL and β-S were increased to 16 μM, PAcP remained constant in the CL treated group (2.94 U/mg prot) while the PAcP of the β-S treated group increased significantly (3.89 U/mg prot). The higher levels of PAcP observed when β-S concentration is increased suggest that differentiation may be involved in the inhibition of prostate cancer cell growth. 16 μM β-S is comparable to levels of phytosterols in the plasma of vegetarians. The differential in growth patterns between the 16 μM β-S and 16 μM CL treatments may partially explain the differences in mortality observed in populations with a high phytosterol intake versus populations with a high intake of animal products.