Title: Silymarin inhibits function of the androgen receptor by reducing nuclearlocalization of the receptor in the human prostate cancer cell line LNCaP.Authors: Zhu W, Zhang JS, Young CY.Source: Carcinogenesis 2001 Sep;22(9):1399-403
Agents with novel mechanisms of blocking androgen receptor (AR) function may be useful for prostate cancer prevention and therapy. Previous studies showed that silibinin (SB), the major active component of Milk Thistle, could inhibit cell proliferation of a human prostate cancer cell line by stopping the cell cycle without causing cell death. This study further demonstrates the potential molecular mechanism by which Milk Thistle acts on androgen-responsive prostate cancer cells by inhibiting function of the AR. We observed that Silymarin (SM) and SB inhibited androgen-stimulated cell proliferation as well as androgen-stimulated secretion of both prostate-specific antigen (PSA) and human glandular kallikrein (hK2).Additionally, for the first time, we show that SM and SB diminished transactivation activity of the AR. However, SM did not affect AR levels and steroid-binding ability of total AR in western blotting and ligand-binding assays. Intriguingly, we found that nuclear AR levels are significantly reduced by SM and SB in the presence of androgens. This study provides a new insight into how Milk Thistle negatively modulates androgen action in prostate cancer cells.