Enhancement of adenoviral MDA-7-mediated cell killing in human lung cancer cells by geldanamycin and its 17-allyl- amino-17-demethoxy analogue.
In: Cancer Gene Therapy, Jg. 14 (2007), Heft 1, S. 12-18
Online
academicJournal
Zugriff:
Our previous studies demonstrated that adenovirus-mediated overexpression of melanoma differentiation-associated gene-7 (Ad-mda7) leads to rapid induction of double-stranded RNA-dependent protein kinase (PKR) and activation of its downstream targets, resulting in apoptosis induction in human lung cancer cells. Here, we report that Ad-mda7 and the benzoquinone ansamycin geldanamycin (GA) interact in a highly synergistic manner to induce cell death in human lung cancer cells. Co-administration of Ad-mda7 and GA did not modify expression of MDA-7, and was not associated with further PKR induction and activation; instead the enhanced cytotoxicity of this combination was associated with inactivation of AKT by GA. By surface staining using anti-E-cadherin monoclonal antibody and flow cytometry, we found that treatment with the combination of Ad-mda7 and GA increased E-cadherin levels in these cancer cells. Ad-mda7 and GA cotreatment also inhibited lung cancer cell motility by increasing the β-catenin/E-cadherin association. Moreover, combination of GA derivative 17-allyl-amino, 17-demethoxygeldanamycin (17AAG), with Ad-mda7 resulted in enhancement of cell death in A549 and H460 human lung cancer cells.Cancer Gene Therapy (2007) 14, 12–18. doi:10.1038/sj.cgt.7700989; published online 6 October 2006 [ABSTRACT FROM AUTHOR]
Titel: |
Enhancement of adenoviral MDA-7-mediated cell killing in human lung cancer cells by geldanamycin and its 17-allyl- amino-17-demethoxy analogue.
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Autor/in / Beteiligte Person: | Pataer, A. ; Bocangel, D. ; Chada, S. ; Roth, J. A. ; Hunt, K. K. ; Swisher, S. G. |
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Zeitschrift: | Cancer Gene Therapy, Jg. 14 (2007), Heft 1, S. 12-18 |
Veröffentlichung: | 2007 |
Medientyp: | academicJournal |
ISSN: | 0929-1903 (print) |
DOI: | 10.1038/sj.cgt.7700989 |
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