Cancer cell injury by cytotoxins from cobra venom is mediated through lysosomal damage
| Autor: | Alexander S. Arseniev, Yuriy N. Utkin, Dmitriy I. Rodionov, Alexei V. Feofanov, M. V. Astapova, George V. Sharonov |
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| Rok vydání: | 2005 |
| Předmět: |
Lung Neoplasms
Time Factors Biological Transport Active Plasma protein binding Adenocarcinoma complex mixtures Biochemistry fluids and secretions Leukemia Promyelocytic Acute Cell Line Tumor Lysosome medicine Animals Humans Cytotoxic T cell Naja kaouthia Cytotoxicity Molecular Biology Elapid Venoms A549 cell Cell Death biology Cytotoxins Cell Membrane Cell Biology bacterial infections and mycoses biology.organism_classification digestive system diseases Cell biology medicine.anatomical_structure Cell culture Immunology Cancer cell bacteria Lysosomes Protein Binding Research Article |
| Zdroj: | Biochemical Journal. 390:11-18 |
| ISSN: | 1470-8728 0264-6021 |
| Popis: | Cytotoxins from cobra venom are known to manifest cytotoxicity in various cell types. It is widely accepted that the plasma membrane is a target of cytotoxins, but the mechanism of their action remains obscure. Using the confocal spectral imaging technique, we show for the first time that cytotoxins from cobra venom penetrate readily into living cancer cells and accumulate markedly in lysosomes. Cytotoxins CT1 and CT2 from Naja oxiana, CT3 from Naja kaouthia and CT1 from Naja haje are demonstrated to possess this property with respect to human lung adenocarcinoma A549 and promyelocytic leukaemia HL60 cells. Immobilized plasma membrane binding accompanies the internalization of CT3 from Naja kaouthia in the HL60 cells, but it is very weak for other cytotoxins. Detectable membrane binding is not a property of any of the cytotoxins tested in A549 cells. The kinetics and concentration-dependence of cytotoxin accumulation in lysosomes correlate well with their cytotoxic effects. On the basis of the results obtained, we propose that lysosomes are a primary target of the lytic action of cytotoxins. Plasma membrane permeabilization seems to be a downstream event relative to lysosome rupture. Direct damage to the plasma membrane may be a complementary mechanism, but its relative contribution to the cytotoxic action depends on the cytotoxin structure and cell type. |
| Databáze: | OpenAIRE |
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