NDLI: Caspases participation in cell death induced by the GD2-specific antibodies

Content Provider	Springer Nature Link
Author	Vishnyakova, P. A. Doronin, I. I. Kholodenko, I. V. Ryazantsev, D. Yu. Molotkovskaya, I. M. Kholodenko, R. V.
Copyright Year	2014
Abstract	Contribution of the main caspases in cytotoxic effects induced by the monoclonal antibody 14G2a specific to the tumor-associated ganglioside GD2 was studied in the EL-4 mouse lymphoma cells. The constitutive expression of the procaspase genes was found in the EL-4 cells. Incubation of the cells with the 14G2a antibodies did not result in increasing of the procaspase synthesis. We also demonstrated with the use of fluorescently labeled substrates of caspases that the procaspase enzymatic activity was not enhanced. At an equal level of cell death, activities of caspase-3 and caspase-9 in the cells which were incubated with the 14G2a antibodies were 7.5 and 3 times lower, respectively, than those in the staurosporine-treated cells. The pan-caspase inhibitor (Z-VAD-FMK) and the caspase-3 inhibitor decreased the cytotoxic effects induced by the 14G2a antibodies by 9–16 and 6–13%, respectively. The staurosporine-induced level of the apoptosis decreased by 55–65% under the same conditions. Inhibitors of the initiation caspase-8 and caspase-9 had no influence on the antibody-induced cell death. The inhibitory analysis also demonstrated that the caspases were not involved in the triggering of the initial stages of the antibody-induced cell death such as apoptotic volume decrease and permeabilization of the cell plasma membrane. Thus, caspases did not play a key role in the cell death induced by the anti-GD2 antibodies, and their slight enzymatic activity did not determine the main mechanism of cell death mediated through the tumor-associated ganglioside GD2.
Starting Page	279
Ending Page	287
Page Count	9
File Format	PDF
ISSN	10681620
Journal	Russian Journal of Bioorganic Chemistry
Volume Number	40
Issue Number	3
e-ISSN	1608330X
Language	English
Publisher	Pleiades Publishing
Publisher Date	2014-05-15
Publisher Place	Moscow
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	GD2 tumor-associated gangliosides caspases cell death apoptosis monoclonal antibodies Biochemistry Bioorganic Chemistry Organic Chemistry Biomedicine general
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Biochemistry

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