Document Detail

Inactivation of H+-vacuolar ATPase by the energy blocker 3-bromopyruvate, a new antitumour agent.
MedLine Citation:
PMID:  16908033     Owner:  NLM     Status:  MEDLINE    
3-bromopyruvate (3-Br PA), a strong alkylating agent, was found to cause a dramatic disruption of pH gradients in acidic compartments of Ehrlich ascites tumour cells (EATCs), as well as of rat thymocytes, at concentrations similar to those reported to cause ATP depletion in hepatocellular carcinoma cells. However, in the condition of complete disruption of pH gradients, ATP depletion was not, in either cell type, as serious as pH gradient dissipation. Moreover, the 3-Br PA effect on acidic compartments preceded severe cell ATP depletion, indicating that the former was not merely linked to energy deprivation elicited by 3-Br PA. Experiments conducted on isolated lysosomes supported this view in that the drug inactivated H(+)-vacuolar ATPase, the enzyme that makes certain compartments in the cell acidic. Inactivation probably involved alkylation of the enzyme on a thiol group, essential for H(+)-ATPase activity for dithiothreitol secured complete protection from 3-Br PA inactivation. The findings are discussed with regards to a possible involvement of lysosome destabilization in 3-Br PA induced cell death.
P Dell'Antone
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Publication Detail:
Type:  Journal Article     Date:  2006-07-05
Journal Detail:
Title:  Life sciences     Volume:  79     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-10-18     Completed Date:  2006-11-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  2049-55     Citation Subset:  IM    
Department of Experimental and Biomedical Sciences, University of Padova, Padova, Italy.
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MeSH Terms
Antineoplastic Agents / pharmacology*
Carcinoma, Ehrlich Tumor
Energy Metabolism / drug effects*
Enzyme Inhibitors / pharmacology*
Hydrogen-Ion Concentration
Liver / cytology
Lysosomes / drug effects*,  enzymology,  metabolism
Pyruvates / pharmacology*
Thymus Gland / cytology
Tumor Cells, Cultured
Vacuolar Proton-Translocating ATPases / antagonists & inhibitors*
Reg. No./Substance:
0/Antineoplastic Agents; 0/Enzyme Inhibitors; 0/Pyruvates; 1113-59-3/bromopyruvate; EC 3.6.1.-/Vacuolar Proton-Translocating ATPases

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