Vacuolar-type ATPases are multicomponent proton pumps involved in the
acidification of single membrane intracellular compartments such as endosomes and
lysosomes. They couple the hydrolysis of ATP to the translocation of one or two
protons across the membrane. Acidification of the lumen of single membrane organelles
is a necessary factor for the correct traffic of membranes and cargo to and from the
different internal compartments of a cell. V-ATPases are also involved in the regulation
of pH at the cytosol and, possibly, extracellular milieu. The inhibition of V-ATPases
has been shown to induce apoptosis as well as cell cycle arrest in tumor cells; therefore,
chemicals that behave as inhibitors of this kind of proton pumps have been proposed as
putative treatment agents against cancer and many have been patented as such. The
compounds filed in patents fall into five major types: plecomacrolides, benzolactone
enamides, archazolids, chondropsins and indoles. All these have proved to be apoptosis
inducers in cell culture and many are able to reduce xenograft tumor growth in murine
models. The present chapter will summarize their general structure, origin and
mechanisms of action and put them in relation to the patents registered so far for the
treatment of cancer.
Keywords: Acidification, apicularen, apoptosis, archazolid, bafilomycin, cell
cycle arrest, cell death, chondropsin, concanamycin, endosome, hidrazide, indole,
lobatamide, lysosome, macrolide, organelle, palmerolide, salicylihalamide, VATPase,
Warburg-effect.