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 journalArticle

26 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

Fingerprint

Flavoproteins
Cells
Light
Oxidative stress
Endosomes
DNA Fragmentation
Cell death
Lysosomes
Lighting
Caspase 3
Ascorbic Acid
Inhibitory Concentration 50
Assays
Neoplasms
Oxidative Stress
Cell Death
Staining and Labeling
DNA
Proteins

Keywords

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

ASJC Scopus subject areas

  • Biochemistry

Cite this

A new anticancer toxin based on HER2/neu-specific DARPin and photoactive flavoprotein miniSOG. / Proshkina, G. M.; Shilova, O. N.; Ryabova, A. V.; Stremovskiy, O. A.; Deyev, S. M.

In: Biochimie, Vol. 118, 09.11.2015, p. 116-122.

Research output: Contribution to journalArticle

Proshkina, G. M. ; Shilova, O. N. ; Ryabova, A. V. ; Stremovskiy, O. A. ; Deyev, S. M. / A new anticancer toxin based on HER2/neu-specific DARPin and photoactive flavoprotein miniSOG. In: Biochimie. 2015 ; Vol. 118. pp. 116-122.
@article{d5615a886db84d198aef8871142cb1f4,
title = "A new anticancer toxin based on HER2/neu-specific DARPin and photoactive flavoprotein miniSOG",
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",
author = "Proshkina, {G. M.} and Shilova, {O. N.} and Ryabova, {A. V.} and Stremovskiy, {O. A.} and Deyev, {S. M.}",
year = "2015",
month = "11",
day = "9",
doi = "10.1016/j.biochi.2015.08.013",
language = "English",
volume = "118",
pages = "116--122",
journal = "Biochimie",
issn = "0300-9084",
publisher = "Elsevier",

}

TY - JOUR

T1 - A new anticancer toxin based on HER2/neu-specific DARPin and photoactive flavoprotein miniSOG

AU - Proshkina, G. M.

AU - Shilova, O. N.

AU - Ryabova, A. V.

AU - Stremovskiy, O. A.

AU - Deyev, S. M.

PY - 2015/11/9

Y1 - 2015/11/9

N2 - 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.

AB - 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.

KW - Blue light illumination

KW - DARPin

KW - HER2/neu

KW - miniSOG

UR - http://www.scopus.com/inward/record.url?scp=84941089642&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941089642&partnerID=8YFLogxK

U2 - 10.1016/j.biochi.2015.08.013

DO - 10.1016/j.biochi.2015.08.013

M3 - Article

VL - 118

SP - 116

EP - 122

JO - Biochimie

JF - Biochimie

SN - 0300-9084

ER -