Antimetastatic effect of a small-molecule vacuolar H+-ATPase inhibitor in in vitro and in vivo preclinical studies
Articolo
Data di Pubblicazione:
2008
Citazione:
Antimetastatic effect of a small-molecule vacuolar H+-ATPase inhibitor in in vitro and in vivo preclinical studies / R. Supino, G. Petrangolini, G. Pratesi, M. Tortoreto, E. Favini, L. Dal Bo, P. Casalini, E. Radaelli, A.C. Croce, G. Bottiroli, P. Misiano, C. Farina, F. Zunino. - In: THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS. - ISSN 0022-3565. - 324:1(2008 Jan), pp. 15-22. [10.1124/jpet.107.128587]
Abstract:
On the basis of the evidence that vacuolar H+-ATPase is implicated in the development of the metastatic phenotype, we have explored the possibility to target the enzyme function in an attempt to control the metastatic behavior of tumor cells. In this study, we used an indole derivative, NiK-12192 [4-(5,6-dichloro-1H-indol-2- yl)-3-ethoxy-N-(2,2,6,6-tetramethyl-piperidin-4-yl)-benzamide], recently identified as an effective inhibitor of vacuolar H+-ATPase, as a potential antimetastatic agent in the treatment of NSCLC H460 xenograft, which is able to induce lung metastases in mice. Oral administration of NiK-12192 caused a significant inhibition of formation of spontaneous metastases. In contrast, the drug exhibited a negligible effect on the development of artificial metastases (i.e., after i.v. injection of tumor cells), thus supporting that the drug affects the early events of the metastatic process ( e. g., migration and invasion). Cellular effects are consistent with this interpretation. In conclusion, the available results show for the first time that a vacuolar H+-ATPase inhibitor is effective in modulation of the metastatic behavior of a lung carcinoma, supporting its potential therapeutic interest as a novel treatment approach.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
human-melanoma cells ; v-atpase ; extracellular ph ; subunit-c ; cancer ; actin ; binding ; metastasis ; expression ; migration
Elenco autori:
R. Supino, G. Petrangolini, G. Pratesi, M. Tortoreto, E. Favini, L. Dal Bo, P. Casalini, E. Radaelli, A.C. Croce, G. Bottiroli, P. Misiano, C. Farina, F. Zunino
Link alla scheda completa: