title: Anti-cancer activity of nitrones in the Apc(Min/+) model of colorectal cancer.
abstract: Abstract The nitrones of alpha-phenyl-tert-butyl nitrone (PBN) and 4-hydroxyl-PBN (4-OH-PBN) that have anti-cancer activity in models of liver cancer and glioblastomas were tested in the ApcMin/+ mouse model. Mice were administered PBN and 4-OH-PBN in drinking water and intestinal tumour size and number assessed after 3-4 months. Throughout the experiment, contrast-enhanced magnetic resonance imaging (MRI) was used to monitor colon tumours. MRI data showed a time-dependent significant increase in total colonic signal intensity in sham-treated mice, but a significant decrease for PBN-treated mice and slight decrease for 4-OHPBN treated mice, probably due to the limited water solubility of 4-OH-PBN. Final pathological and percentage survival data agreed with the MRI data. PBN had little effect on oxaliplatin-mediated killing of HCT116 colon cancer cells and caused only a slight decrease in the amount of active fraction caspase 3 in oxaliplatin-treated cells. PBN has significant anti-cancer activity in this model of intestinal neoplasia.
authors.affiliation: Experimental Therapeutics Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. robert-floyd@omrf.org
authors.forename: Robert A
authors.initials: RA
authors.lastname: Floyd
authors.forename: Rheal A
authors.initials: RA
authors.lastname: Towner
authors.forename: Dee
authors.initials: D
authors.lastname: Wu
authors.forename: Andrew
authors.initials: A
authors.lastname: Abbott
authors.forename: Rebecca
authors.initials: R
authors.lastname: Cranford
authors.forename: Dan
authors.initials: D
authors.lastname: Branch
authors.forename: Wei-Xing
authors.initials: WX
authors.lastname: Guo
authors.forename: Steven B
authors.initials: SB
authors.lastname: Foster
authors.forename: Inna
authors.initials: I
authors.lastname: Jones
authors.forename: Rajib
authors.initials: R
authors.lastname: Alam
authors.forename: Danny
authors.initials: D
authors.lastname: Moore
authors.forename: Toby
authors.initials: T
authors.lastname: Allen
authors.forename: Mark
authors.initials: M
authors.lastname: Huycke
mesh_terms: D000236:Adenoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D017491:Genes, APC; D045325:HCT116 Cells; D006801:Humans; D019656:Loss of Heterozygosity / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009589:Nitrogen Oxides / Q000494:pharmacology* / Q000627:therapeutic use; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D009589:Nitrogen Oxides; C015388:nitrones