Anti-cancer activity of nitrones in the Apc^Min/+ model of colorectal cancer

Abstract

The nitrones of α-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.

Keywords::

• Nitrones
• HCT-116 cells
• Apc^Min/+ mice
• colorectal cancer
• oxaliplatin

Acknowledgements

Research was supported in part by Oklahoma Applied Research Support (OARS) grant AR052-041, NIH RO1CA82506, Oklahoma Center for the Advancement of Science & Technology (OCAST) fMRI.002, Department of Veterans Affairs Merit Review Program, and the Frances Duffy Endowment. Robert A. Floyd is Merrick Foundation Chair in Aging research. We thank Donna Howell for aid with graphics and document development.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This paper was first published online on Early Online on 19 October 2009