Adenoviral endoplasmic reticulum-targeted mda-7/interleukin-24 vector enhances human cancer cell killing.

Molecular Cancer Therapeutics
Abujiang PataerStephen G Swisher

Abstract

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.

References

Apr 27, 1999·The International Journal of Biochemistry & Cell Biology·R JagusG N Barber
Apr 21, 2001·Cell Death and Differentiation·G N Barber
Sep 21, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·L DumoutierJ C Renauld
Dec 26, 2001·Science's STKE : Signal Transduction Knowledge Environment·B R Williams
Apr 4, 2002·Trends in Immunology·Helmut FickenscherHeinrich Sticht
Jun 11, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eva G CaudellElizabeth A Grimm
Mar 10, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Kerry A SiegerSunil Chada
May 4, 2004·International Immunopharmacology·Rahul V GopalkrishnanPaul B Fisher
May 4, 2004·International Immunopharmacology·Sunil ChadaAbner M Mhashilkar
Nov 27, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Sunil ChadaSuhendan Ekmekcioglu
Apr 27, 2005·Molecular Therapy : the Journal of the American Society of Gene Therapy·Abujiang PataerStephen G Swisher
Dec 24, 2005·Apoptosis : an International Journal on Programmed Cell Death·R KimS Murakami
Jan 7, 2006·Cell Death and Differentiation·J Wu, R J Kaufman

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Citations

Feb 2, 2013·Cancer Gene Therapy·P LamB-A Guinn
Feb 2, 2013·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Chengcheng GuoApar Pataer
Oct 12, 2010·Cytokine & Growth Factor Reviews·Rupesh DashPaul B Fisher
Feb 9, 2010·Trends in Molecular Medicine·Stefan Grimm, Mathieu Noteborn
Apr 24, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Baobiao ZhuoYingchun Shi

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