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.
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Research Article|
August 09 2005
Cancer cell injury by cytotoxins from cobra venom is mediated through lysosomal damage
Alexei V. Feofanov;
Alexei V. Feofanov
1
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997, Moscow, Russia
1To whom correspondence should be addressed (email alexei@nmr.ru).
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George V. Sharonov;
George V. Sharonov
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997, Moscow, Russia
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Maria V. Astapova;
Maria V. Astapova
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997, Moscow, Russia
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Dmitriy I. Rodionov;
Dmitriy I. Rodionov
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997, Moscow, Russia
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Yuriy N. Utkin;
Yuriy N. Utkin
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997, Moscow, Russia
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Alexander S. Arseniev
Alexander S. Arseniev
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997, Moscow, Russia
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Publisher: Portland Press Ltd
Received:
November 15 2004
Revision Received:
March 18 2005
Accepted:
April 25 2005
Accepted Manuscript online:
April 25 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 390 (1): 11–18.
Article history
Received:
November 15 2004
Revision Received:
March 18 2005
Accepted:
April 25 2005
Accepted Manuscript online:
April 25 2005
Citation
Alexei V. Feofanov, George V. Sharonov, Maria V. Astapova, Dmitriy I. Rodionov, Yuriy N. Utkin, Alexander S. Arseniev; Cancer cell injury by cytotoxins from cobra venom is mediated through lysosomal damage. Biochem J 15 August 2005; 390 (1): 11–18. doi: https://doi.org/10.1042/BJ20041892
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