Radiation-sensitising effects of antennapedia proteins (ANTP)-SmacN7 on tumour cells

Int J Mol Sci. 2013 Dec 11;14(12):24087-96. doi: 10.3390/ijms141224087.

Abstract

The objective of this study was to investigate the underlying mechanisms behind the radiation-sensitising effects of the antennapedia proteins (ANTP)-smacN7 fusion protein on tumour cells. ANTP-SmacN7 fusion proteins were synthesised, and the ability of this fusion protein to penetrate cells was observed. Effects of radiation on the expression of X-linked inhibitor of apoptosis protein (XIAP) were detected by western blotting. The radiation-sensitising effects of ANTP-SmacN7 fusion proteins were observed by a clonogenic assay. The effects of drugs and radiation on tumour cell apoptosis were determined using Annexin V/FITC double staining. Changes in caspase-8, caspase-9 and caspase-3 were detected by western blot before and after ANTP-SmacN7 inhibition of XIAP. The ANTP-SmacN7 fusion protein could enter and accumulate in cells; in vitro XIAP expression of radiation-induced tumour cells was negatively correlated with tumour radiosensitivity. The ANTP-SmacN7 fusion protein promoted tumour cell apoptosis through the activation of caspase3. ANTP-SmacN7 fusion protein may reduce tumour cell radioresistance by inducing caspase3 activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antennapedia Homeodomain Protein / chemistry
  • Antennapedia Homeodomain Protein / genetics
  • Antennapedia Homeodomain Protein / metabolism*
  • Apoptosis / drug effects*
  • Apoptosis / radiation effects
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Fluorescent Dyes / chemistry
  • Gamma Rays
  • HeLa Cells
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Molecular Sequence Data
  • Oligopeptides / chemistry
  • Oligopeptides / genetics
  • Oligopeptides / metabolism*
  • Permeability / drug effects
  • Permeability / radiation effects
  • Radiation Tolerance / drug effects*
  • Radiation-Sensitizing Agents / chemistry
  • Radiation-Sensitizing Agents / metabolism
  • Radiation-Sensitizing Agents / pharmacology*
  • Receptors, Death Domain / metabolism
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / pharmacology
  • X-Linked Inhibitor of Apoptosis Protein / antagonists & inhibitors
  • X-Linked Inhibitor of Apoptosis Protein / metabolism

Substances

  • Antennapedia Homeodomain Protein
  • Fluorescent Dyes
  • Oligopeptides
  • Radiation-Sensitizing Agents
  • Receptors, Death Domain
  • Recombinant Fusion Proteins
  • SMAC peptide
  • X-Linked Inhibitor of Apoptosis Protein
  • Caspase 3
  • Caspase 9