Article
Intracellular proton pumps as targets in chemotherapy: V-ATPases and cancer
Author/s | Hernández López, Agustín
Serrano Bueno, Gloria Pérez Castiñeira, José Román Serrano Delgado, Aurelio |
Department | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular |
Publication Date | 2012 |
Deposit Date | 2019-04-03 |
Published in |
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Abstract | 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 ... 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), toghether with other transporters, are responsible to a great extent for these symptoms. These multisubunit 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 determined to play an important role in the acidification of the intercellular medium. This importance makes them an attractive target for control of tumour cells. In the present review we portray the major characteristics of this kind of proton pumps, we provide some recent insights on their in vivo regulation, an overview of the consequences that V-ATPase inhibition carries for the tumour cell, such as cell cycle arrest or cell death, and a brief summary of the studies related to cancer made recently with commercially available inhibitors for this kind of proton pump. Some new approaches to affect V-ATPase function are also suggested in the light of recent knowledge on the regulation of this proton pump. |
Project ID. | PAIDI
BIO-261 P07-CVI-3082 BFU2007-61887 BFU2010-15622 |
Citation | Hernández López, A., Serrano Bueno, G., Pérez Castiñeira, J.R. y Serrano Delgado, A. (2012). Intracellular proton pumps as targets in chemotherapy: V-ATPases and cancer. Current Pharmaceutical Design, 18 (10), 1383-1394. |
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