Intraorganellar acidification by V-ATPases: a target in cellproliferation and cancer therapy
2010
Hernández López, Agustín | Serrano Bueno, Gloria | Herrera Palau, Rosana | Pérez Castiñeira, José Román | Serrano Delgado, Aurelio | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular
V-ATPases are multicomponent proton pumps involved in the acidification of singlemembrane intracellular compartments such as endosomes and lysosomes. They couple thehydrolysis of ATP to the translocation of one to two protons across the membrane. Acidification ofthe lumen of single membrane organelles is a necessary factor for the correct traffic of membranesand cargo to and from the different internal compartments of a cell. Also, V-ATPases are involved inregulation of pH at the cytosol and, possibly, extracellular milieu. The inhibition of V-ATPases hasbeen shown to induce apoptosis and cell cycle arrest in tumour cells and, therefore, chemicals thatbehave as inhibitors of this kind of proton pumps have been proposed as putative treatment agentsagainst cancer. The present review will summarize the major types of V-ATPase inhibitors and theirmechanisms of action and put them in relation to the patents registered so far for the treatment of cancer.
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