Document Detail


Intracellular Proton Pumps as Targets in Chemotherapy: V-ATPases and Cancer.
MedLine Citation:
PMID:  22360554     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cancer cells show a metabolic shift that makes them overproduce protons; this has the potential to disturb the cellular acid-base homeostasis. However, these cells show cytoplasmic alkalinisation, increased acid extrusion and endosome-dependent drug resistance. Vacuolar type ATPases (V-ATPases), together with other transporters, are responsible to a great extent for these symptoms. These multi-subunit proton pumps are involved in the control of cytosolic pH and the generation of proton gradients (positive inside) across endocellular membrane systems like Golgi, endosomes or lysosomes. In addition, in tumours, they have been shown to play an important role in the acidification of the intercellular medium. This importance makes them an attractive target to control tumour cell proliferation. In the present review we present the major characteristics of this kind of proton pumps and we provide some recent insights on their in vivo regulation. Also, we review some of the consequences that V-ATPase inhibition carries for the tumour cell, such as cell cycle arrest or cell death, and provide a brief summary of the studies related to cancer made recently with commercially available inhibitors. In the light of recent knowledge on the regulation of this proton pump, some new approaches to impair V-ATPase function are also suggested.
Authors:
Agustín Hernández; Gloria Serrano-Bueno; José R Pérez-Castiñeira; Aurelio Serrano
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-23
Journal Detail:
Title:  Current pharmaceutical design     Volume:  -     ISSN:  1873-4286     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9602487     Medline TA:  Curr Pharm Des     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
IBVF-CSIC, Avda. Americo Vespucio 49, 41092 Seville, Spain. agustin.hernandez@ibvf.csic.es.
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