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

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.