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.