Despite recent advances in understanding the
biological basis of
prostate cancer, management of the disease, especially in the phase resistant to
androgen ablation, remains a significant challenge. The long latency and high incidence of prostate
carcinogenesis provides the opportunity to intervene with
chemoprevention to prevent or eradicate prostate
malignancies. In this study, we have used human
hormone-resistant
prostate cancer cells, DU145 and PC3, as an in vitro model to assess the efficacy of
xanthohumol (XN) against cell growth, motility and invasion. We observed that treatment of
prostate cancer cells with low micromolar doses of XN inhibits proliferation and modulates
focal adhesion kinase (FAK) and AKT phosphorylation leading to reduced cell migration and invasion. Oxidative stress by increased production of
reactive oxygen species (ROS) was associated with these effects. Transgenic
adenocarcinoma of the mouse prostate (TRAMP) transgenic mice were used as an in vivo model of prostate
adenocarcinoma. Oral gavage of XN, three times per week, beginning at 4 wks of age, induced a decrease in the average weight of the urogenital (UG) tract, delayed advanced
tumor progression and inhibited the growth of poorly differentiated prostate
carcinoma. The ability of XN to inhibit
prostate cancer in vitro and in vivo suggests that XN may be a novel agent for the management of
prostate cancer.