Adenoviral endoplasmic reticulum-targeted mda-7/interleukin-24 vector enhances human cancer cell killing
Authors
Pataer, AbujiangHu, Wenxian
Xiaolin, Lu
Chada, Sunil
Roth, Jack A.
Hunt, Kelly K.
Swisher, Stephen G.
UMass Chan Affiliations
Department of Thoracic and Cardiovascular SurgeryDepartment of Molecular Genetics and Microbiology
Graduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2008-08-30Keywords
Adenoviridae; Animals; Cell Line, Tumor; Endoplasmic Reticulum; Female; Fluorescent Antibody Technique; *Genetic Vectors; Interleukins; Mice; Mice, Nude; NeoplasmsLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
We developed several adenoviral vectors designed to target MDA-7 expression to different subcellular compartments [endoplasmic reticulum (ER), mitochondria, nucleus, and cytosol] and evaluated their ability to enhance apoptosis. Adenoviral ER-targeted mda-7/interleukin-24 vector (Ad-ER-mda7) selectively and effectively inhibited the growth and proliferation of lung (A549 and H1299) and esophageal (Seg1 and Bic1) cancer cells by enhancing cell killing. Both Ad-mda7 and Ad-ER-mda7 activated a novel pathway of ER stress-induced apoptosis characterized by unregulated expression of phosphorylated JNK, phosphorylated c-Jun, and phosphorylated RNA-dependent protein kinase. Caspase-4 activation mediated Ad-mda7- and Ad-ER-mda7-induced cell death. In addition, Ad-mda7- and Ad-ER-mda7-mediated growth inhibition correlated with activation of ER molecular markers RNA-dependent protein kinase and JNK both in vitro (in Ad-mda7- or Ad-ER-mda7-treated lung cancer cells) and in vivo. These findings suggest that vectors targeting the ER (Ad-ER-mda7) may be more effective in cancer gene therapy possibly through more effective induction or ER stress pathways.Source
Mol Cancer Ther. 2008 Aug;7(8):2528-35. Link to article on publisher's siteDOI
10.1158/1535-7163.MCT-08-0083Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33035PubMed ID
18723497; 18723497Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1158/1535-7163.MCT-08-0083