Recombinant prostate-specific antigen proaerolysin shows selective protease sensitivity and cell cytotoxicity

Ravibhushan Singh, Jeff L. Browning, Ralph Abi-Habib, Kevin Wong, Simon A. Williams, Rosemina Merchant, Samuel R. Denmeade, Thomas J. Buckley, Arthur E. Frankel

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Native proaerolysin is a channel-forming bacterial protoxin that binds to cell-surface receptors and then is activated by furin or furin-like proteases. We genetically engineered proaerolysin by replacing the furin-cleavage sequence with a prostate-specific antigen-selective sequence. The recombinant modified proaerolysin was expressed and purified from Aeromonas salmonicida in good yields and purity. Recombinant modified proaerolysin had no furin sensitivity and markedly increased prostate-specific antigen sensitivity relative to wild-type proaerolysin. Human prostate cancer cells were significantly more sensitive to recombinant modified proaerolysin in the presence of active prostate-specific antigen when compared with the absence of prostate-specific antigen or the presence of potent prostate-specific antigen inhibitors. Most normal human cells with the exception of prostate and renal epithelial cells showed very low sensitivity to recombinant modified proaerolysin. Our results suggest that recombinant modified proaerolysin is a potent prostate-specific antigen-sensitive protoxin that deserves further development for regional therapy of benign and malignant prostate growths.

Original languageEnglish (US)
Pages (from-to)809-816
Number of pages8
JournalAnti-Cancer Drugs
Volume18
Issue number7
DOIs
StatePublished - Aug 1 2007

Keywords

  • Proaerolysin
  • Prostate cancer
  • Prostate-specific antigen

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Cancer Research

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    Singh, R., Browning, J. L., Abi-Habib, R., Wong, K., Williams, S. A., Merchant, R., Denmeade, S. R., Buckley, T. J., & Frankel, A. E. (2007). Recombinant prostate-specific antigen proaerolysin shows selective protease sensitivity and cell cytotoxicity. Anti-Cancer Drugs, 18(7), 809-816. https://doi.org/10.1097/CAD.0b013e3280bad82d