GSH depletion enhances adenoviral bax-induced apoptosis in lung cancer cells

Tsuyoshi Honda, Simona Coppola, Lina Ghibelli, Song H. Cho, Shunsuke Kagawa, Kevin B. Spurgers, Shawn M. Brisbay, Jack A. Roth, Raymond E. Meyn, Bingliang Fang, Timothy J. McDonnell

Research output: Contribution to journalArticle

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Abstract

The utility of dominant acting proapoptotic molecules to induce cell death in cancer cells is being evaluated in preclinical studies and clinical trials. We recently developed a binary adenoviral expression system to enable the efficient gene transfer of Bax and other proapoptotic molecules. Using this system, overexpression of Bax protein in four non-small-cell lung cancer (NSCLC) cell lines, H1299, A549, H226 and H322, was evaluated. The H322 line exhibited significant resistance to Bax-induced cell death compared to the other cell lines. H322 cells had the highest level of glutathione (GSH). GSH levels were significantly decreased following buthionine sulfoximine treatment and this coincided with enhanced apoptosis induction by Ad-Bax in H322 cells. GSH depletion enhanced Bax protein translocation to mitochondrial membranes. These findings suggest that the redox status may be a determinant of Bax-mediated cell death and that manipulation of intracellular thiols may sensitize cells to apoptosis by facilitating Bax insertion into mitochondrial membranes.

Original languageEnglish
Pages (from-to)249-255
Number of pages7
JournalCancer Gene Therapy
Volume11
Issue number4
DOIs
Publication statusPublished - Apr 2004
Externally publishedYes

Fingerprint

Lung Neoplasms
Apoptosis
bcl-2-Associated X Protein
Cell Death
Mitochondrial Membranes
Buthionine Sulfoximine
Protein Transport
Sulfhydryl Compounds
Non-Small Cell Lung Carcinoma
Oxidation-Reduction
Glutathione
Clinical Trials
Cell Line
Genes
Neoplasms

Keywords

  • Apoptosis
  • Bax
  • Glutathione
  • Redox

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Honda, T., Coppola, S., Ghibelli, L., Cho, S. H., Kagawa, S., Spurgers, K. B., ... McDonnell, T. J. (2004). GSH depletion enhances adenoviral bax-induced apoptosis in lung cancer cells. Cancer Gene Therapy, 11(4), 249-255. https://doi.org/10.1038/sj.cgt.7700684

GSH depletion enhances adenoviral bax-induced apoptosis in lung cancer cells. / Honda, Tsuyoshi; Coppola, Simona; Ghibelli, Lina; Cho, Song H.; Kagawa, Shunsuke; Spurgers, Kevin B.; Brisbay, Shawn M.; Roth, Jack A.; Meyn, Raymond E.; Fang, Bingliang; McDonnell, Timothy J.

In: Cancer Gene Therapy, Vol. 11, No. 4, 04.2004, p. 249-255.

Research output: Contribution to journalArticle

Honda, T, Coppola, S, Ghibelli, L, Cho, SH, Kagawa, S, Spurgers, KB, Brisbay, SM, Roth, JA, Meyn, RE, Fang, B & McDonnell, TJ 2004, 'GSH depletion enhances adenoviral bax-induced apoptosis in lung cancer cells', Cancer Gene Therapy, vol. 11, no. 4, pp. 249-255. https://doi.org/10.1038/sj.cgt.7700684
Honda, Tsuyoshi ; Coppola, Simona ; Ghibelli, Lina ; Cho, Song H. ; Kagawa, Shunsuke ; Spurgers, Kevin B. ; Brisbay, Shawn M. ; Roth, Jack A. ; Meyn, Raymond E. ; Fang, Bingliang ; McDonnell, Timothy J. / GSH depletion enhances adenoviral bax-induced apoptosis in lung cancer cells. In: Cancer Gene Therapy. 2004 ; Vol. 11, No. 4. pp. 249-255.
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