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

Cancer Gene Therapy volume 11, pages 249–255 (2004)Cite this article

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.

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Acknowledgements

This work was supported by NIH Grants PO1 CA78778 and RO1 CA69003. Song Cho and Kevin Spurgers were supported by NIH training Grant T32 CA67759.

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Authors and Affiliations

  1. Department of Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USA

    Tsuyoshi Honda, Song H Cho, Kevin B Spurgers, Shawn M Brisbay & Timothy J McDonnell

  2. Institut tor Vergata Rome, Italy

    Simona Coppola & Lina Ghibelli

  3. Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USA

    Shunsuke Kagawa, Jack A Roth & Bingliang Fang

  4. Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, 77030, Texas, USA

    Raymond E Meyn

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  1. Tsuyoshi Honda
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Correspondence to Timothy J McDonnell.

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Honda, T., Coppola, S., Ghibelli, L. et al. GSH depletion enhances adenoviral bax-induced apoptosis in lung cancer cells. Cancer Gene Ther 11, 249–255 (2004). https://doi.org/10.1038/sj.cgt.7700684

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