A new anticancer toxin based on HER2/neu-specific DARPin and photoactive flavoprotein miniSOG

Biochimie. 2015 Nov:118:116-22. doi: 10.1016/j.biochi.2015.08.013. Epub 2015 Aug 28.

Abstract

Cytotoxic effects of a new targeted phototoxin DARPin-miniSOG and mechanism of its action were investigated in vitro. It was determined that DARPin-miniSOG causes light-induced death of HER2/neu-positive cancer cells (IC50 0.8 μM). Treatment of the cells with DARPin-miniSOG in the presence of ascorbic acid eliminated the light-induced cytotoxic action of the protein. This observation suggests the involvement of oxidative stress in the mechanism of the phototoxin action. DNA fragmentation analysis, caspase-3 activity assay and PI-staining of HER2/neu-positive cancer cells treated with DARPin-miniSOG indicated that phototoxin induces necrotic cell death under blue light illumination. Co-localization analysis showed that DARPin-miniSOG accumulates mostly in endosomes and lysosomes.

Keywords: Blue light illumination; DARPin; HER2/neu; miniSOG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Blotting, Western
  • CHO Cells
  • Cell Death / drug effects
  • Cricetulus
  • Flavoproteins / pharmacology
  • Humans
  • Microscopy, Confocal
  • Oxidative Stress
  • Phototherapy / methods*
  • Phototropins / pharmacology
  • Receptor, ErbB-2 / metabolism*
  • Recombinant Fusion Proteins / pharmacology*
  • Surface Plasmon Resonance

Substances

  • Antineoplastic Agents
  • Flavoproteins
  • Phototropins
  • Recombinant Fusion Proteins
  • ERBB2 protein, human
  • Receptor, ErbB-2