Antimetastatic effect of a small molecule vacuolar H+-ATPase inhibitor in in vitro and in vivo preclinical studies. (Articolo in rivista)

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Label
  • Antimetastatic effect of a small molecule vacuolar H+-ATPase inhibitor in in vitro and in vivo preclinical studies. (Articolo in rivista) (literal)
Anno
  • 2008-01-01T00:00:00+01:00 (literal)
Alternative label
  • Supino R, Petrangolini G, Pratesi G, Tortoreto M, Favini E, Dal Bo L, Casalini P, Radaelli E, Croce AC, Bottiroli G, Misiano P, Farina C, Zunino F. (2008)
    Antimetastatic effect of a small molecule vacuolar H+-ATPase inhibitor in in vitro and in vivo preclinical studies.
    in The Journal of pharmacology and experimental therapeutics (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Supino R, Petrangolini G, Pratesi G, Tortoreto M, Favini E, Dal Bo L, Casalini P, Radaelli E, Croce AC, Bottiroli G, Misiano P, Farina C, Zunino F. (literal)
Pagina inizio
  • 15 (literal)
Pagina fine
  • 22 (literal)
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  • 324 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#note
  • doi:10.1124/jpet.107.128587 (literal)
Note
  • ISI Web of Science (WOS) (literal)
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  • (SR; PeG; PrG, TM; FE;BLD; CP; ZF) Fondazione IRCCS Istituto Nazionale Tumori, Milan, and (RE) Facoltà Medicina Veterinaria Università Studi di Milano, Milan, Italy; (BG; CAC) Istochemistry and Cytometry section, Institute of Molecular Genetics, Consiglio Nazionale delle Ricerche, 27100 Pavia,Italy; (MP; FC) Nikem Research, Baranzate, Milan, Italy. (literal)
Titolo
  • Antimetastatic effect of a small molecule vacuolar H+-ATPase inhibitor in in vitro and in vivo preclinical studies. (literal)
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 behaviour 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 antimetastic 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. following i.v. injection of tumor cells), thus supporting that the drug affect 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 behaviour of a lung carcinoma, supporting its potential therapeutic interest as a novel treatment approach. (literal)
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