Induction of apoptosis by gene transfer of human TRAIL mediated by arginine-rich intracellular delivery peptides

Anticancer Res. 2010 Jun;30(6):2193-202.

Abstract

Background: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor (TNF) family, has shown potent and high selective antitumor activity as a promising therapy for cancer. We have developed an arginine-rich intracellular delivery (AID) peptide-mediated system for nontoxic and efficient gene transfer in cells.

Materials and methods: To evaluate antitumor activity and therapeutic potential of TRAIL gene, a bifunctional expression plasmid was constructed encoding the secretory signal peptide of human immunoglobulin kappa (Ig kappa) light chain, the extracellular portion (amino acids 95-281) of human TRAIL and the humanized green fluorescent protein (GFP).

Results: We demonstrated that AID peptides were able to effectively deliver TRAIL gene into human lung carcinoma A549 cells. Soluble TRAIL-GFP protein purified from media after gene delivery was further evaluated regarding selective induction of apoptosis in cells.

Conclusion: AID peptide-mediated DNA transfer provides a potential and convenient tool in nonviral gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Arginine
  • Cell Line, Tumor
  • Drug Delivery Systems
  • Flow Cytometry
  • Genetic Therapy*
  • Green Fluorescent Proteins / genetics
  • Humans
  • In Situ Nick-End Labeling
  • Neoplasms / therapy*
  • Peptides / administration & dosage*
  • Plasmids
  • TNF-Related Apoptosis-Inducing Ligand / genetics*

Substances

  • Peptides
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Green Fluorescent Proteins
  • Arginine