title: Prostate secretory protein (PSP94) suppresses the growth of androgen-independent prostate cancer cell line (PC3) and xenografts by inducing apoptosis.
abstract: BACKGROUND
  PSP94 (prostate secretory protein of 94 aa; also called PIP), one of the predominant proteins secreted into the seminal fluid, was proposed as an independent diagnostic/prognostic marker for prostate cancers. It was also shown to inhibit rat prostate cancer growth. In this study, we investigated the effect of purified PSP94 on the growth of androgen-independent human prostate cancer cells (PC3) and its potential mechanism of action.
  
  
  RESULTS
  PSP94, in a dose- and time-dependent manner, inhibited the growth of PC3 cells. The protein demonstrated a stronger inhibitory effect on the colony-forming ability of PC3 cells in soft agar. A daily injection of PSP94 at 5 microg/kg/body weight resulted in a 50-60% inhibition in the growth of PC3 xenografts in athymic mice. PC3 cell growth inhibition by PSP94 resulted from cell death characteristic of morphological apoptosis, which was confirmed by dual fluorescence microscopy, electron microscopy, and DNA fragmentation assays. Mechanistic studies indicated that PSP94 enhanced the expression of proapoptotic protein Bax without affecting Bcl-2 levels.
  
  
  CONCLUSIONS
  This study suggests that PSP94 may represent a novel, apoptosis-based, antitumor agent applicable to the treatment of hormone-refractory human prostate cancers.
authors.affiliation: Procyon Biopharma, Inc., London, Ontario, Canada.
authors.forename: S V
authors.initials: SV
authors.lastname: Garde
authors.forename: V S
authors.initials: VS
authors.lastname: Basrur
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: M A
authors.initials: MA
authors.lastname: Finkelman
authors.forename: A
authors.initials: A
authors.lastname: Krishan
authors.forename: L
authors.initials: L
authors.lastname: Wellham
authors.forename: E
authors.initials: E
authors.lastname: Ben-Josef
authors.forename: M
authors.initials: M
authors.lastname: Haddad
authors.forename: J D
authors.initials: JD
authors.lastname: Taylor
authors.forename: A T
authors.initials: AT
authors.lastname: Porter
authors.forename: D G
authors.initials: DG
authors.lastname: Tang
mesh_terms: D000728:Androgens; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D002999:Clone Cells / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D029584:Prostatic Secretory Proteins; D051381:Rats; D013997:Time Factors; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured