title: Effects of the potential chemopreventive agent DMU-135 on adenoma development in the ApcMin+ mouse.
abstract: DMU-135 (3,4-Methylenedioxy-3',4',5'-trimethoxy chalcone) is a novel anticancer prodrug designed to be activated into a potent tyrosine kinase inhibitor by the tumour selective enzyme activity of the cytochrome P450 enzyme CYP1B1. CYP1B1 is selectively expressed in a wide variety of tumours including colon. The hypothesis was tested that DMU-135 would inhibit Apc(Min/+) mouse gastrointestinal adenoma formation. From 4-18 weeks of age animals received DMU-135 (0.2% w:w) in AIN93G diet. DMU-135 was well tolerated, induced no systemic side-effects and reduced adenoma multiplicity by 46 +/- 18.3% compared to controls (p < 0.001). Further characterisation of this promising chemopreventive agent is required.
authors.affiliation: Cancer Biomarkers and Prevention Group, Department of Cancer Studies, University of Leicester, Leicester, UK.
authors.forename: S
authors.initials: S
authors.lastname: Sale
authors.forename: R G
authors.initials: RG
authors.lastname: Tunstall
authors.forename: K C
authors.initials: KC
authors.lastname: Ruparelia
authors.forename: P C
authors.initials: PC
authors.lastname: Butler
authors.forename: G A
authors.initials: GA
authors.lastname: Potter
authors.forename: W P
authors.initials: WP
authors.lastname: Steward
authors.forename: A J
authors.initials: AJ
authors.lastname: Gescher
mesh_terms: D000236:Adenoma / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D017491:Genes, APC; D006400:Hematocrit; D007414:Intestinal Neoplasms / Q000473:pathology / Q000517:prevention & control*; D007421:Intestine, Small / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D011355:Prodrugs / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors
chemical_list: C523254:3,4-methylenedioxy-3',4',5'-trimethoxy chalcone; D000970:Antineoplastic Agents; D011355:Prodrugs; D002599:Chalcone; D011505:Protein-Tyrosine Kinases