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

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 language	English
Pages (from-to)	116-122
Number of pages	7
Journal	Biochimie
Volume	118
DOIs	https://doi.org/10.1016/j.biochi.2015.08.013
Publication status	Published - 9 Nov 2015
Externally published	Yes

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Keywords

Blue light illumination
DARPin
HER2/neu
miniSOG

ASJC Scopus subject areas

Biochemistry

Cite this

Proshkina, G. M., Shilova, O. N., Ryabova, A. V., Stremovskiy, O. A., & Deyev, S. M. (2015). A new anticancer toxin based on HER2/neu-specific DARPin and photoactive flavoprotein miniSOG. Biochimie, 118, 116-122. https://doi.org/10.1016/j.biochi.2015.08.013

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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.}",

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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

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KW - HER2/neu

KW - miniSOG

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10.1016/j.biochi.2015.08.013