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 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.
Supino
Rosanna
R
Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, Milano, Italy. rosanna.supino@istitutotumori.mi.it
Scovassi
A Ivana
AI
Croce
Anna Cleta
AC
Dal Bo
Laura
L
Favini
Enrica
E
Corbelli
Alessandro
A
Farina
Carlo
C
Misiano
Paola
P
Zunino
Franco
F
D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D045325:HCT116 Cells; D018922:HL-60 Cells; D019073:HT29 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008247:Lysosomes / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D019030:Receptors, Vitronectin / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism
C514015:4-(5,6-dichloro-1H-indol-2-yl)-3-ethoxy-N-(2,2,6,6-tetramethylpiperidin-4-yl)benzamide; D001549:Benzamides; D007211:Indoles; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5; D025262:Vacuolar Proton-Translocating ATPases