Anti-cancer activity of nitrones in the Apc(Min/+) model of colorectal cancer.
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.
Floyd
Robert A
RA
Experimental Therapeutics Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. robert-floyd@omrf.org
Towner
Rheal A
RA
Wu
Dee
D
Abbott
Andrew
A
Cranford
Rebecca
R
Branch
Dan
D
Guo
Wei-Xing
WX
Foster
Steven B
SB
Jones
Inna
I
Alam
Rajib
R
Moore
Danny
D
Allen
Toby
T
Huycke
Mark
M
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
D000970:Antineoplastic Agents; D009589:Nitrogen Oxides; C015388:nitrones