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Investigational New Drugs
Published in: Investigational New Drugs 6/2014

01-12-2014 | PRECLINICAL STUDIES

A novel AMPK activator reduces glucose uptake and inhibits tumor progression in a mouse xenograft model of colorectal cancer

Authors: Silvia Valtorta, Gabriella Nicolini, Farida Tripodi, Cristina Meregalli, Guido Cavaletti, Federica Avezza, Luca Crippa, Gloria Bertoli, Francesca Sanvito, Paola Fusi, Roberto Pagliarin, Fulvia Orsini, Rosa Maria Moresco, Paola Coccetti

Published in: Investigational New Drugs | Issue 6/2014

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Summary

The anticancer activity of a novel pure 1,4-Diaryl-2-azetidinone (1), endowed with a higher solubility than the well known Combretastatin A4, is tested in mice. We previously reported that Compound (1) showed specific antiproliferative activity against duodenal and colon cancer cells, inducing activation of AMP-activated protein kinase and apoptosis. Here we estimate that the maximum tolerated dose in a mouse model is 40 mg/kg; the drug is well tolerated both in single dose and in repeated administration schedules. The drug displays a significant antitumor activity and a tumor growth delay when administered at the MTD both in single and fractionated i.v. administration in a mouse xenograft model of colorectal cancer. Arrest of tumor growth and relapse after drug suspension are parallel to modification in glucose demand as shown by PET studies with [18 F] FDG. These data strongly support Compound (1) as a promising molecule for in vivo treatment of colorectal cancer.
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Metadata
Title
A novel AMPK activator reduces glucose uptake and inhibits tumor progression in a mouse xenograft model of colorectal cancer
Authors
Silvia Valtorta
Gabriella Nicolini
Farida Tripodi
Cristina Meregalli
Guido Cavaletti
Federica Avezza
Luca Crippa
Gloria Bertoli
Francesca Sanvito
Paola Fusi
Roberto Pagliarin
Fulvia Orsini
Rosa Maria Moresco
Paola Coccetti
Publication date
01-12-2014
Publisher
Springer US
Published in
Investigational New Drugs / Issue 6/2014
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI
https://doi.org/10.1007/s10637-014-0148-8

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