Piper cubeba targets multiple aspects of the androgen-signalling pathway : a potential phytotherapy against prostate cancer growth?

Despite the high prevalence of prostate cancer (PC) in the Western world, there is a dearth of effective medication. Since the androgen-signalling pathway is very much involved in PC growth and development, we investigated the potential of Piper cubeba L. extract, P9605, in targeting multiple events simultaneously within this pathway. This may be more effective compared to an antiandrogen monotherapy. Our results indicated that P9605 inhibited proliferation in androgen-dependent LNCaP human prostate cancer cells by reducing DNA synthesis and inducing apoptosis. This antigrowth effect was less pronounced in androgen-independent PC-3 prostate cancer cell lines. P9605 potently inhibited 5 alpha-reductase II activity, which is responsible for converting testosterone to its active form, dihydrotestosterone (DHT), in the prostate. It also acted as an antagonist at recombinant wild-type androgen receptors (AR). P9605 suppressed cell growth and prostate-specific antigen (PSA) secretion stimulated by physiological concentrations of DHT in LNCaP cells. Interestingly, it down-regulated AR levels. In conclusion, our findings suggest that P9605 may potentially retard the growth of androgen-dependent PC via several mechanisms.