BIOACTIVITIES OF HOP-DERIVED PRENYLFLAVONOIDS IN RELATION TO PROSTATE CANCER

Prostate cancer (PC) is highly common among aging men causing bothersome symptoms or developing into a life-threatening disease. Phytoestrogens could influence hormone-dependent diseases including PC by their varying bio-activities. Recently, five prenylflavonoids xanthohumol (X), desmethylxanthohumol (DMX), isoxanthohumol (IX), 8-prenylnaringenin (8PN), and 6-prenylnaringenin (6PN) were identified in hops (Humulus lupulus L.) which were investifated in this research project for their chemopreventive or therapeutic properties on PC. The compounds were found to inhibit the proliferation of the human prostate cancer cells PC-3, DU145, and LNCaP.FGC in a dose-dependent manner. Antiproliferative activities of X and 6PN were found to be strongest for PC-3 and DU145, while, on LNCaP.FGC, these compounds first exerted a strong induction of cell proliferation followed by a proliferation shut-off. 8PN, which has previously been identified as a highly potent phytoestrogen, showed weaker antiproliferative effects on PC-3 and DU145. However, on LNCaP.FGC, 8PN demonstrated a more potent growth inhibition. IX exhibited activities on PC-3 and DU145 comparable to those of 8PN, but it was more effective on LNCaP.FGC. DMX was the least active compound in all cell lines. No quantitative relation between the estrogenic potency as measured in the recombinant yeast estrogen screen and antiproliferative effects could be concluded. The strong antiproliferative activity of X in endothelial cells suggests potential antiangiogenic activity compromising tumor growth and metastasis. Further research into the underlying mechanisms of growth inhibition revealed that there was no evidence for induction of apoptotic cell death in PC-3 and DU145 upon treatment with X, IX, 8PN, and 6PN. However, considering the formation of vacuoles in PC-3 when treated with IX and 6PN, and in DU145 when treated with IX, 6PN, and 8PN, it is suggested that autophagy is induced, which could consequently lead to cell death in this model. It can be concluded that X, IX, 8PN, and 6PN appear to be promising candidates for further investigation in prostate anticancer therapy and chemoprevention, especially in the final stages