title: APC10.1 cells as a model for assessing the efficacy of potential chemopreventive agents in the Apc(Min) mouse model in vivo.
abstract: Apc(Min) mice are widely used for mechanism and efficacy studies associated with the development of chemopreventive agents. APC10.1 cells have been derived from Apc(Min) mouse adenomas and retain the heterozygous Apc genotype. We tested the hypothesis that this cell type may provide an in vitro model to predict chemopreventive activity of agents in the Apc(Min) mouse in vivo. The growth inhibitory properties of 14 putative colorectal cancer chemopreventive agents, tricin, apigenin, 3',4',5',5,7-pentamethoxyflavone, resveratrol, curcumin, 3,4-methylenedioxy-3',4',5'-trimethoxychalcone (DMU135), 3,4,5,4'-tetramethoxystilbene (DMU212), celecoxib, aspirin, piroxicam, all-trans-retinoic acid, difluoromethylornithine (DFMO), quercetin and cyanidin-3-glucoside, were studied in this cell line, and the IC(50) values were calculated. The IC(50) values were plotted against previously published data of reduction of adenoma numbers caused by these agents in Apc(Min) mice. The correlation co-efficient was 0.678 (p<0.01), suggesting that there was a tentative correlation between the ability to inhibit the growth of APC10.1 cells and the ability to delay adenoma development in vivo. If this relationship is supported by using further agents, APC10.1 cells may serve in the future as an initial screen to prioritise compounds for assessing chemopreventive efficacy in Apc(Min) mice in vivo. Such a screen could reduce the number of animals required to find active agents, help reduce costs and increase throughput.
authors.affiliation: Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester Royal Infirmary, Leicester LE2 7LX, UK. sls13@le.ac.uk
authors.forename: Stewart
authors.initials: S
authors.lastname: Sale
authors.forename: Isabel L
authors.initials: IL
authors.lastname: Fong
authors.forename: Carla
authors.initials: C
authors.lastname: de Giovanni
authors.forename: Lorena
authors.initials: L
authors.lastname: Landuzzi
authors.forename: Karen
authors.initials: K
authors.lastname: Brown
authors.forename: William P
authors.initials: WP
authors.lastname: Steward
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Gescher
mesh_terms: D000236:Adenoma / Q000517:prevention & control*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D020128:Inhibitory Concentration 50; D051379:Mice; D014407:Tumor Cells, Cultured
chemical_list: D016588:Anticarcinogenic Agents