Publications [#177515] of Bruce A Sullenger

Papers Published

1. J Mi, X Zhang, Y Liu, SK Reddy, ZN Rabbani, BA Sullenger, BM Clary, NF-kappaB inhibition by an adenovirus expressed aptamer sensitizes TNFalpha-induced apoptosis., Biochemical and biophysical research communications, vol. 359 no. 3 (August, 2007), pp. 475-80, ISSN 0006-291X [doi]
   (last updated on 2010/07/15)

   Abstract:
   Prolonged activation of NF-kappaB is involved in the pathogenesis of chronic inflammatory diseases and associated cancers. NF-kappaB activation is considered to be a main mechanism opposing TNFalpha-induced apoptosis. We investigated whether inhibition of NF-kappaB could sensitize tumor and endothelial cells to TNFalpha-induced apoptosis. As such, we developed a novel H1 RNA polymerase III promoter driven adenoviral vector to express an RNA aptamer, Ad-A-p50, which selectively inhibits NF-kappaB activation in the nucleus. This event sensitizes human lung adenocarcinoma cells (A549) and human endothelial cells (HUVEC) to TNFalpha-induced apoptosis through the multiple pathways regulated by NF-kappaB, including Bcl-XL, HIF-1alpha, and VEGF. Our findings also suggest a new mechanism of HIF-1alpha regulation by NF-kappaB in the normoxic environment. RNA aptamer inhibition of NF-kappaB offers exciting opportunities for sensitizing inflammatory and tumor cells to TNFalpha-induced apoptosis.

   Keywords:
   Adenoviridae • Apoptosis • Aptamers, Nucleotide • Base Sequence • Cells, Cultured • Down-Regulation • Endothelial Cells • Humans • Molecular Sequence Data • NF-kappa B • Neoplasms • Tumor Necrosis Factor-alpha • cytology • drug effects • drug effects* • genetics* • metabolism • metabolism* • pathology • pharmacology*