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PMID: 20459683 Published · epublish English Journal Article Research Support, Non-U.S. Gov't Review

Proton pump inhibitors as anti vacuolar-ATPases drugs: a novel anticancer strategy.

Journal of experimental & clinical cancer research : CR ·Vol. 29 ·2010-05-08 ·Pages 44

Spugnini EP, Citro G, Fais S

Abstract

The vacuolar ATPases are ATP-dependent proton pumps whose functions include the acidification of intracellular compartments and the extrusion of protons through the cell cytoplasmic membrane. These pumps play a pivotal role in the regulation of cell pH in normal cells and, to a much greater extent, in tumor cells. In fact, the glucose metabolism in hypoxic conditions by the neoplasms leads to an intercellular pH drift towards acidity. The acid microenvironment is modulated through the over-expression of H+ transporters that are also involved in tumor progression, invasiveness, distant spread and chemoresistance. Several strategies to block/downmodulate the efficiency of these transporters are currently being investigated. Among them, proton pump inhibitors have shown to successfully block the H+ transporters in vitro and in vivo, leading to apoptotic death. Furthermore, their action seems to synergize with conventional chemotherapy protocols, leading to chemosensitization and reversal of chemoresistance. Aim of this article is to critically revise the current knowledge of this cellular machinery and to summarize the therapeutic strategies developed to counter this mechanism.

MeSH Terms
Antineoplastic Agents/therapeutic use Cytoplasm/metabolism Disease Progression Gene Expression Regulation Humans Neoplasm Invasiveness Neoplasm Metastasis Neoplasms/drug therapy,enzymology Proton Pump Inhibitors/therapeutic use Proton Pumps/metabolism Vacuolar Proton-Translocating ATPases/antagonists & inhibitors,metabolism
Chemicals
Antineoplastic Agents Proton Pump Inhibitors Proton Pumps Vacuolar Proton-Translocating ATPases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Spugnini Enrico P
S.A.F.U. Department, Regina Elena Cancer Institute, Rome, Italy.
Citro Gennaro
Fais Stefano
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Article Info
Journal
Journal of experimental & clinical cancer research : CR
Abbr.
J Exp Clin Cancer Res
ISSN
1756-9966
DOI
10.1186/1756-9966-29-44
Published
2010-05-08
Epub
2010-00-08
Pages
44
Language
English
Region
England
NLM ID
8308647
PMCID
PMC2876100
Subset
IM
External Links
PubMed source DOI: 10.1186/1756-9966-29-44 PMC Full Text View journal details
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