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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.

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Authors and Affiliations

  1. Cancer Biomarkers and Prevention Group, Department of Cancer Studies, University of Leicester, Leicester, UK

    S. Sale, R. G. Tunstall, W. P. Steward & A. J. Gescher

  2. Cancer Drug Discovery Group, School of Pharmacy, DeMontfort University, Leicester, UK

    K. C. Ruparelia, P. C. Butler & G. A. Potter

  3. Department of Oral and Dental Sciences, University of Bristol, Bristol Dental Hospital, Bristol, BS1 2LY, UK

    S. Sale

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  1. S. Sale
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  2. R. G. Tunstall
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  3. K. C. Ruparelia
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  4. P. C. Butler
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  5. G. A. Potter
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  6. W. P. Steward
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  7. A. J. Gescher
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Correspondence to S. Sale.

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

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Sale, S., Tunstall, R.G., Ruparelia, K.C. et al. Effects of the potential chemopreventive agent DMU-135 on adenoma development in the ApcMin+ mouse. Invest New Drugs 24, 459–464 (2006). https://doi.org/10.1007/s10637-006-5947-0

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  • DOI: https://doi.org/10.1007/s10637-006-5947-0

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