Involvement of Actin Filaments in the Cytotoxic Effect of GD2-Specific Antibodies

Induction of direct cell death is one of the mechanisms of the antitumor effect of GD2-specific antibodies used for the therapy of high-risk neuroblastoma. The mechanisms of the cytotoxic signal triggered by antibody binding to GD2 ganglioside on the surface of the tumor cell remain insufficiently s...

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Bibliographic Details
Published in:Bulletin of experimental biology and medicine 2019-02, Vol.166 (4), p.541-547
Main Authors: Doronin, I. I., Kholodenko, I. V., Zubareva, A. A., Yarygin, K. N., Deev, S. M., Kholodenko, R. V.
Format: Article
Language:English
Subjects:
Actin
Actin Cytoskeleton - metabolism
Analysis
Animals
Antibodies
Antibodies - immunology
Antibodies - pharmacology
Antitumor activity
Apoptosis
Apoptosis - drug effects
Apoptosis - immunology
Biochemistry
Biomedical and Life Sciences
Biomedicine
Biopharmaceuticals
Cell Biology
Cell death
Cell Line, Tumor
Cell survival
Cytochalasin D
Cytochalasin D - pharmacology
Cytotoxicity
Deoxyribonucleic acid
DNA
Filaments
Gangliosides
Gangliosides - antagonists & inhibitors
Gangliosides - immunology
Humans
Immunoglobulins
Internal Medicine
Laboratory Medicine
Mice
Microfilaments
Muscle proteins
Neuroblastoma
Pathology
Signal Transduction - drug effects
Signal Transduction - immunology
Translated from Kletochnye Tekhnologii v Biologii i Meditsine (Cell Technologies in Biology and Medicine)
Tumor cell lines
Tumors
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Summary:Induction of direct cell death is one of the mechanisms of the antitumor effect of GD2-specific antibodies used for the therapy of high-risk neuroblastoma. The mechanisms of the cytotoxic signal triggered by antibody binding to GD2 ganglioside on the surface of the tumor cell remain insufficiently studied. Using inhibitor analysis we demonstrated that actin microfilaments are involved in the cell death induced by GD2-specific antibodies. Specifically, a strong antagonistic influence of cytochalasin D on the cytotoxic effect induced by GD2-specific antibodies was demonstrated in GD2+ tumor cell lines, which was expressed in at least 20% increase in cell survival and a significant decrease of the fraction of cells with fragmented DNA.
ISSN:0007-4888
1573-8221
DOI:10.1007/s10517-019-04389-0