A recombinant defective adenoviral agent expressing anti-bcl-2 ribozyme promotes apoptosis of bcl-2-expressing human prostate cancer cells

Thambi Dorai*, Harris Perlman, Kenneth Walsh, Ahmad Shabsigh, Erik T. Goluboff, Carl A. Olsson, Ralph Buttyan

*Corresponding author for this work

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Over-expression of bcl-2, a potent anti-apoptosis protein, is likely to be one of the genetic mechanisms through which human prostate cancer cells develop resistance to hormonal and other forms of therapy. To develop a therapeutic agent for hormone-resistant prostate cancer based on suppression of bcl-2 expression, we had previously designed and synthesized a dual- hammerhead ribozyme capable of recognizing and specifically cleaving human bcl-2 mRNA in vitro as well as in vivo. To increase the efficiency by which the anti-bcl-2 ribozyme can be delivered to target cells, we have created a recombinant replication-deficient (defective) adenoviral agent capable of expressing the anti-bcl-2 ribozyme upon infection. This viral agent effectively reduces intracellular levels of bcl-2 mRNA and protein in cultured LNCaP prostate cancer cells following standard infection procedures. Likewise, the defective adenovirus-anti-bcl-2 ribozyme induces extensive apoptosis in several androgen-sensitive (LNCaP) and androgen-insensitive (LNCaP/bcl-2 and PC-3) human prostate cancer cell lines that express differing amounts of bcl-2 protein. One androgen-insensitive prostate cancer cell line, DU-145, lacking in bcl-2 expression, was found to be completely refractory to the effects of the virus ribozyme, supporting the concept that the cytotoxic effects of the ribozyme are based solely on its effects on bcl- 2 expression. Our results support further development of this adenovirus/anti-bcl-2 ribozyme for potential gene therapeutic purposes in certain forms of hormone-resistant prostate cancer where over-expression of bcl-2 proto-oncogene is indicated.

Original languageEnglish (US)
Pages (from-to)846-852
Number of pages7
JournalInternational Journal of Cancer
Volume82
Issue number6
DOIs
StatePublished - 1999

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'A recombinant defective adenoviral agent expressing anti-bcl-2 ribozyme promotes apoptosis of bcl-2-expressing human prostate cancer cells'. Together they form a unique fingerprint.

Cite this