A recombinant adenovirus expressing wild-type bax induces apoptosis in prostate cancer cells independently of their Bcl-2 status and androgen sensitivity

Tsuyoshi Honda, Shunsuke Kagawa, Kevin B. Spurgers, Bjorn T. Gjertsen, Jack A. Roth, Bingliang Fang, Stephanie L. Lowe, James S. Norris, Raymond E. Meyn, Timothy J. McDonnell

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Using a binary co-transfection strategy of Ad/GT Bax and Ad/PGK-GV16, we have succeeded in inducing overexpression of Bax protein in three prostate cell lines (androgen-insensitive DU145 and PC3, and androgen-sensitive LNCaP). The expression of Bax protein by this system was sufficient to induce all three prostate lines to undergo apoptosis. The fact that DU145 cells which have a p53 mutation and are deficient in Bax, responded to this treatment, suggests that this effect is independent of these pathways. Initiation of the cleavage of Caspase-3 (CPP32/Yama/apopain) and PARP (poly (ADP-ribose) polymerase) by the introduction of Bax were confirmed by western blot analysis. Bcl-2 expression is relevant in the progression of prostate cancer and contributes to an androgen, apoptotic-resistant phenotype in the advanced stages. We examined stable Bcl-2 overexpressing DU145, PC3 and LNCaP cell lines as models of advanced prostate cancer. The adenoviral co-transfection system induced Bax protein expression and apoptosis even in these Bcl-2 transfected cell lines. Taken together, our results suggest that this Bax expression system might represent a useful gene therapy strategy when applied to the treatment of prostate cancer and its efficacy would be independent of the Bcl-2 status and androgen sensitivity of these cancers.

Original languageEnglish
Pages (from-to)163-167
Number of pages5
JournalCancer Biology and Therapy
Volume1
Issue number2
DOIs
Publication statusPublished - Jan 1 2002
Externally publishedYes

Keywords

  • Adenoviral
  • Androgen
  • Apoptosis
  • Bax
  • Bcl-2
  • Caspase
  • Prostate

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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    Honda, T., Kagawa, S., Spurgers, K. B., Gjertsen, B. T., Roth, J. A., Fang, B., Lowe, S. L., Norris, J. S., Meyn, R. E., & McDonnell, T. J. (2002). A recombinant adenovirus expressing wild-type bax induces apoptosis in prostate cancer cells independently of their Bcl-2 status and androgen sensitivity. Cancer Biology and Therapy, 1(2), 163-167. https://doi.org/10.4161/cbt.63