Document Detail

Lonidamine cytotoxicity: involvement of the lysosomal compartment.
MedLine Citation:
PMID:  11191720     Owner:  NLM     Status:  MEDLINE    
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.
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    
Department of Experimental and Biomedical Sciences, University of Padova, Italy.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Acridine Orange
Antineoplastic Agents / pharmacology*
Carcinoma, Ehrlich Tumor / drug therapy*,  metabolism*
Cell Compartmentation
Energy Metabolism
Enzyme Inhibitors / pharmacology
Glucose / metabolism
Hydrogen-Ion Concentration
Indazoles / pharmacology*
Lysosomes / drug effects*,  metabolism*
Mice, Inbred BALB C
Proton-Translocating ATPases / antagonists & inhibitors
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 ATPases

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

Previous Document:  Suppressive effect of sarpogrelate hydrochloride on respiratory failure and right ventricular failur...
Next Document:  Autologous serum deprivation restored IL-1 receptor antagonist production by peripheral blood mononu...