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

G. M. Proshkina, O. N. Shilova, A. V. Ryabova, O. A. Stremovskiy, S. M. Deyev

Research output: Contribution to journal › Article › peer-review

31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)116-122
Number of pages7
JournalBiochimie
Volume118
DOIs
Publication statusPublished - 9 Nov 2015
Externally publishedYes

Keywords

  • Blue light illumination
  • DARPin
  • HER2/neu
  • miniSOG

ASJC Scopus subject areas

  • Biochemistry

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