Cancer cell injury by cytotoxins from cobra venom is mediated through lysosomal damage
- 9 August 2005
- journal article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 390 (1), 11-18
- https://doi.org/10.1042/bj20041892
Abstract
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.Keywords
This publication has 40 references indexed in Scilit:
- “Weak Toxin” from Naja kaouthia Is a Nontoxic Antagonist of α7 and Muscle-type Nicotinic Acetylcholine ReceptorsOnline Journal of Public Health Informatics, 2001
- Conformational Change and Inactivation of Membrane Phospholipid-Related Activity of Cardiotoxin V from Taiwan Cobra Venom at Acidic pHBiochemistry, 1996
- X-ray Structure at 1·55 Å of Toxin γ, a Cardiotoxin from Naja nigricollis Venom: Crystal Packing Reveals a Model for Insertion into MembranesJournal of Molecular Biology, 1994
- Three-dimensional structures of neurotoxins and cardiotoxinsChemical Research in Toxicology, 1993
- Cobra venom cardiotoxin (cytotoxin) isoforms and neurotoxin: Comparative potency of protein kinase C inhibition and cancer cell cytotoxicity and modes of enzyme inhibitionBiochemistry, 1993
- Ablation of natural killer cell function by soluble cardiotoxinInternational Journal of Immunopharmacology, 1990
- Selective cytolysis by a protein toxin as a consequence of direct interaction with the lymphocyte plasma membraneToxicology and Applied Pharmacology, 1990
- Binding of cardiotoxin analogue III from Formosan cobra venom to FL cellsFEBS Letters, 1986
- Cobra polypeptide cytotoxin I and marine worm polypeptide cytotoxin A-IV are potent and selective inhibitors of phospholipid-sensitive Ca2+-dependent protein kinaseFEBS Letters, 1983
- Properties of association of cardiotoxin with lipid vesicles and natural membranes A fluorescence studyFEBS Letters, 1978