V-ATPase Inhibitors in Cancer Treatment and Their Implication in Multidrug Resistance in Oral Squamous Cell Carcinoma

ATPases are enzyme systems that originated in a common ancestor and are distributed universally among all organisms. There are three types of ATPases: those found in archaea (A-ATPases), synthases (F-APTases), and vacuole or vacuolar ATPases (V-ATPases) (Nelson, Nelson 1989). They are essential for life and have in common the fact that they create an electrochemical ion gradient across the membrane to hydrolyze or synthesize ATP. Structurally, they are enzymatic complexes that work as molecular rotary motors. ATPases are formed by two domains, a hydrophobic domain (A0, V0, and F0) and a hydrophilic domain (A1, V1, and F1) connected by a central axis and either one or two lateral axes. In this chapter, we are going to discuss V-ATPases.