V-ATPase inhibitors and implication in cancer treatment
Received 9 June 2009; received in revised form 3 August 2009; accepted 6 August 2009. published online 16 September 2009.
Summary
Acidity is one of the main features of the tumors. The V-ATPase is the primary responsible for the control of tumor microenvironment by proton extrusion to the extracellular medium. The acid environment favors tissue damage, activation of destructive enzymes in the extracellular matrix, the acquisition of metastatic cell phenotypes as well as increasing the destructive capacity. The application of specific inhibitors of V-ATPases, can decrease the acidity of tumor and may allow the reduction of tumor metastasis, acting on the survival of tumor cells and prevent the phenomena of chemoresistance. Among the most important inhibitors can be distinguished benzolactone enamides (salicylihalamide), lobatamide A and B, apicularen, indolyls, oximidine, macrolactone archazolid, lobatamide C, and cruentaren. The latest generation of inhibitors includes NiK12192, FR202126, and PPI SB 242784. The purpose of this paper is to describe the latest advances in the field of V-ATPase inhibitors, describe further developments related to the classic inhibitors, and discuss new potential applications of these drugs in cancer treatment.
aEntrerríos s/n, Santiago de Compostela C.P. 15782, Spain
bUnidad de Medicina Molecular - Fundación Pública Galega de Medicina Xenómica, Edificio de Consultas planta -2, Hospital Clinico Universitario C.P. 15706, Santiago de Compostela, Spain
Corresponding author. Address: Facultad de Odontología, Entrerríos s/n, Santiago de Compostela C.P. 15782, Spain. Tel.: +34 626233504; fax: +34 986295424.