, Volume 24, Issue 6, pp 459-464

Effects of the potential chemopreventive agent DMU-135 on adenoma development in the ApcMin+ mouse

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Summary

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 ApcMin/+ 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.

Grant support: Programme grant from the UK Medical Research Council and project grant from the Association for International Cancer Research