Prostate secretory protein (PSP94) suppresses the growth of androgen-independent prostate cancer cell line (PC3) and xenografts by inducing apoptosis

BACKGROUND. PSP94 (prostate secretory protein of 94 aa; also called PIP), o ne of the predominant proteins secreted into the seminal fluid, was propose d as an independent diagnostic/prognostic marker for prostate cancers. it w as also shown to inhibit rat prostate cancer growth. in this study, we inve stigated the effect of purified PSP94 on the growth of androgen-independent human prostate cancer cells (PC3) and its potential mechanism of action. METHODS AND RESULTS. PSP94, in a dose- and time-dependent manner, inhibited the growth of PC3 cells. The protein demonstrated a stronger inhibitory ef fect on the colony-forming ability of PC3 cells in soft agar. A daily injec tion of PSP94 at 5 mu g/kg/body weight resulted in a 50-60% inhibition in t he growth of PC3 xenografts in athymic mice. PW cell growth inhibition by P SP94 resulted from cell death characteristic of morphological apoptosis, wh ich was confirmed by dual fluorescence microscopy, electron microscopy, and DNA fragmentation,assays. Mechanistic studies indicated that PSP94 enhance d the expression of pro-apoptotic protein Bar without affecting Bcl-2 level s. CONCLUSIONS. This study suggests that PSP94 may represent a novel, apoptosi s-based, antitumor agent applicable to the treatment of hormone-refractory human prostate cancers. (C) 1999 Wiley-Liss, Inc.