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Ann N Y Acad Sci. 2009 Aug;1171:606-16. doi: 10.1111/j.1749-6632.2009.04705.x.

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

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1
Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale Tumori, Milano, Italy. rosanna.supino@istitutotumori.mi.it

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.

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