nik-12192 and Colonic-Neoplasms

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 alphavbeta5 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.

Topics: Apoptosis; Autophagy; Benzamides; Cell Adhesion; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Dose-Response Relationship, Drug; Flow Cytometry; HCT116 Cells; HL-60 Cells; HT29 Cells; Humans; Hydrogen-Ion Concentration; Indoles; Inhibitory Concentration 50; Lysosomes; Membrane Potential, Mitochondrial; Microscopy, Confocal; Microscopy, Electron; Phagosomes; Receptors, Vitronectin; Vacuolar Proton-Translocating ATPases