Prostate Cancer Intervention Using A Flavonoid Antioxidant, Silymarin

The oncogenic potential of advanced and androgen- independent prostate cancer (PCA) is causally associated with a ligand/receptor autocrine growth loop e.g., interaction of transforming growth factor-alpha (TGFalpha) and epidermal growth factor receptor (erbB 1). It is rationalized that targeting this pathway would be useful for PCA intervention. This (AMC Cancer Research Center) work shows that a flavonoid antioxidant, silymarin, inhibits erbB 1 activation followed by a G 1 arrest and inhibition of PCA cell growth. Additional studies define cause-and- effect relationship for the observed effect of silymarin at the membrane receptor and cytoplasmic levels. Treatment of LNCaP and DU145 human prostate carcinoma cells with silibinin (the pure form of silymarin) results in highly-significant inhibition of TGFalpha binding to erbBE 1 receptor, and ligand internalization, in both dose- and time-dependent manners. Conversely, silibinin does not result in the inhibition of intrinsic tyrosine kinase activity of erbB 1 in both LNCaP and DU145 cells.