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

Abstract

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.

• Authors: Rosanna Supino, A Ivana Scovassi, Anna Cleta Croce, Laura Dal Bo, Enrica Favini, Alessandro Corbelli, Carlo Farina, Paola Misiano, Franco Zunino
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1171 Pg. 606-16 (Aug 2009) ISSN: 1749-6632 [Electronic] United States
• PMID: 19723111 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-(5,6-dichloro-1H-indol-2-yl)-3-ethoxy-N-(2,2,6,6-tetramethylpiperidin-4-yl)benzamide
• Benzamides
• Indoles
• Receptors, Vitronectin
• integrin alphaVbeta5
• Vacuolar Proton-Translocating ATPases

Topics

• Apoptosis (drug effects)
• Autophagy (drug effects)
• Benzamides (pharmacology)
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colonic Neoplasms (metabolism, pathology, ultrastructure)
• Dose-Response Relationship, Drug
• Flow Cytometry
• HCT116 Cells
• HL-60 Cells
• HT29 Cells
• Humans
• Hydrogen-Ion Concentration (drug effects)
• Indoles (pharmacology)
• Inhibitory Concentration 50
• Lysosomes (chemistry, drug effects, metabolism)
• Membrane Potential, Mitochondrial (drug effects)
• Microscopy, Confocal
• Microscopy, Electron
• Phagosomes (drug effects, metabolism, ultrastructure)
• Receptors, Vitronectin (metabolism)
• Vacuolar Proton-Translocating ATPases (antagonists & inhibitors, metabolism)