Biological effects of a new v-H-ATPase inhibitor in colon carcinoma cell lines.

Vacuolar-H+-ATPase plays a critical role in the cellular balance of protons thus regulating intracellular pH and contributing to apoptosis resistance, drug resistance and invasive and metastatic behaviour of cells NiK-12192, a Vacuolar-H+-ATPase inhibitor, caused a reduction in the volume and/or acidity of lysosomes, a polarization of ±v²5 integrin distribution, and a number of floating alive cells whereas signs of apoptosis appeared only after 72 h of treatment In conclusion, NiK-12192, by affecting Vacuolar- H+-ATPase activity (and intracellular pH) causes a modification of structures crucial for the cell adhesion and induces cell death likely by a modality involving an anoikis-mediated apoptosis