20(S)-Protopanaxadiol-Aglycone Downregulates Full-Length and Ligand-Independent Splice Variants of Androgen Receptor

The study provided evidence that ginsenoside 20(S)-protopanaxadiol-aglycone (PPD) effectively downregulated the expression and activity of androgen receptors, including both full-length and ligand-independent splice variants, in prostate cancer cells. This downregulation was achieved through proteasome-mediated degradation and resulted in a reduction of androgen receptor protein and mRNA levels. The study also demonstrated the in vivo preclinical efficacy of PPD in inhibiting the growth of androgen receptor-expressing prostate cancer cells and reducing the expression of prostate-specific antigen. These findings suggested that PPD could be a promising chemopreventive agent for prostate cancer, addressing the limitations of existing treatments like finasteride and dutasteride, particularly in cancers with high levels of ligand-independent androgen receptor variants.