BIological effects of a new vacuolar-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 behavior of cells. NiK-12192, a vacuolar-H+-ATPase inhibitor, caused a reduction in the volume and/or acidity of lysosomes, a polarization of αvβ5 integrin distribution, and a number of floating live 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 cell adhesion and induces cell death, likely by a modality involving an anoikis-mediated apoptosis. © 2009 New York Academy of Sciences.