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

Seema V. Garde, Vathsala S. Basrur, Li Li, Malcolm A. Finkelman, Awtar Krishan, Larry Wellham, Edgar Ben-Josef, Maher Haddad, John D. Taylor, Arthur T. Porter, Dean G. Tang

Research output: Contribution to journalArticle

58 Scopus citations

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. METHODS AND 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 μg/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.

Original languageEnglish (US)
Pages (from-to)118-125
Number of pages8
JournalProstate
Volume38
Issue number2
DOIs
StatePublished - Feb 3 1999

Keywords

  • Apoptosis
  • Clonogenecity
  • Prostate cancer
  • PSP94

ASJC Scopus subject areas

  • Urology

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    Garde, S. V., Basrur, V. S., Li, L., Finkelman, M. A., Krishan, A., Wellham, L., Ben-Josef, E., Haddad, M., Taylor, J. D., Porter, A. T., & Tang, D. G. (1999). Prostate secretory protein (PSP94) suppresses the growth of androgen- independent prostate cancer cell line (PC3) and xenografts by inducing apoptosis. Prostate, 38(2), 118-125. https://doi.org/10.1002/(SICI)1097-0045(19990201)38:2<118::AID-PROS5>3.0.CO;2-G