Chemopreventative properties of cruciferous vegetable extracts and purified components for human prostate cancer.

摘要

A recent case-control epidemiological study has shown a significant reduction (41%) in the risks of developing prostate cancer among men who consume at least three servings of cruciferous vegetables (e.g. broccoli, cabbage, watercress, brussel sprouts) per week. We are investigating mechanisms of chemoprevention by cruciferous vegetables aside from known Phase II enzyme manifestation and carcinogen metabolism. This research addresses the effects of extracts and purified glucosinolates, isothiocyanates, and indoles from cruciferous vegetables on malignant (PC-3, DU145, and LNCaP) and prostatic epithelial cell growth and function. The ultimate goal of this research is to illustrate a means of lowering prostate cancer risks by consumption of cruciferous vegetables and to identify the components that have biological activity that can be linked to chemoprevention for human and animal studies. Both extracts and purified isothiocyanates from cruciferous vegetables inhibit cell proliferation, arrest cell cycle progression, and induce apoptosis in each of the three studied malignant cell lines in a dose dependent manner. The most potent extracts in growth inhibition were the broccoli sprout extract (S phase arrest) and watercress extract (G₂M phase arrest), as we observed a greater concentration of isothiocyanates in these extracts. The most potent isothiocyanates were benzyl isothiocyanate, sulforaphane, and phenethyl isothiocyanate with IC₅₀ values between 2.3 and 9.8 μM. Purified glucosinolates and indoles were less effective in the growth inhibitory effects with IC ₅₀ values over 100 μM. Sulforaphane, benzyl isothiocyanate, and phenethyl isothiocyanate were able to induce apoptosis in each line by 12%, 45%, and 54% respectively after 72 hours. Human prostatic epithelial cells (non-malignant) were much more resistant to the growth inhibitory effects and pro-apoptotic effects of isothiocyanates up to 50 μM concentrations. Insulin like growth factor (IGF-1) was added to AT6.3 (rat prostate) cells and their proliferation increased 3.4-fold. Isothiocyanates sulforaphane, phenethyl, and benzyl isothiocyanate inhibited IGF-1 stimulated cell proliferation and induced apoptosis in the cells at concentrations under 5 μM. Ultimately, this research shows that compounds from cruciferous vegetables can lower cancer risks by a variety of mechanisms such as proliferation inhibition, induction of apoptosis, and through influencing signal transduction pathways in malignant prostate cells.