Document Detail


Lonidamine cytotoxicity: involvement of the lysosomal compartment.
MedLine Citation:
PMID:  11191720     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Lonidamine (LND) was found to decrease significantly the pH gradient across intracellular compartments in Ehrlich ascites tumour cells. The effect was maximal in the range 0.2 - 0.3 mM LND, and was observed both in the presence of glucose - i.e. conditions in which a high bioenergetic status of the cells was maintained by glycolysis (due to a strong Crabtree effect in these cells) - and in the absence of glucose. Moreover the LND effect was also observed in the presence of bafilomycin, a specific inhibitor of the H+ -vacuolar ATP-ase. Based on these findings, we suggest that the LND effect on the proton gradient reflects an LND-induced increase in membrane proton conductance. The consequent impairment of intracellular proton gradients might be involved in the mechanism of action of LND, allowing drugs that are weak bases to accumulate preferentially in the cytoplasm and nucleus.
Authors:
P Dell'Antone; M Bragadin; L Piergallini
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of international medical research     Volume:  28     ISSN:  0300-0605     ISO Abbreviation:  J. Int. Med. Res.     Publication Date:    2000 Nov-Dec
Date Detail:
Created Date:  2001-01-12     Completed Date:  2001-03-15     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0346411     Medline TA:  J Int Med Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  269-76     Citation Subset:  IM    
Affiliation:
Department of Experimental and Biomedical Sciences, University of Padova, Italy.
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MeSH Terms
Descriptor/Qualifier:
Acridine Orange
Animals
Antineoplastic Agents / pharmacology*
Carcinoma, Ehrlich Tumor / drug therapy*,  metabolism*
Cell Compartmentation
Energy Metabolism
Enzyme Inhibitors / pharmacology
Glucose / metabolism
Glycolysis
Hydrogen-Ion Concentration
Indazoles / pharmacology*
Lysosomes / drug effects*,  metabolism*
Male
Mice
Mice, Inbred BALB C
Proton-Translocating ATPases / antagonists & inhibitors
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Enzyme Inhibitors; 0/Indazoles; 50-99-7/Glucose; 50264-69-2/lonidamine; 65-61-2/Acridine Orange; EC 3.6.3.14/Proton-Translocating ATPases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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