Regular Article

British Journal of Cancer (2001) 85, 1585–1591. doi:10.1054/bjoc.2001.2142 www.bjcancer.com
Published online 13 November 2001

Lycobetaine acts as a selective topoisomerase IIbold beta poison and inhibits the growth of human tumour cells

H U Barthelmes2, E Niederberger1, T Roth4, K Schulte1, W C Tang1, F Boege2, H-H Fiebig3,4, G Eisenbrand1 and D Marko1

  1. 1Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Erwin-Schroedinger Str. 52, Kaiserslautern, 67663
  2. 2Medizinische Poliklinik, University of Würzburg Medical School, Klinikstr. 6–8, Würzburg, 97070
  3. 3Tumor Biology Center at the University of Freiburg, Breisacher Str. 117, Freiburg i. Br., 79106
  4. 4Institute for Experimental Oncology, Oncotest GmbH, Am Flughafen 8–10, Freiburg i. Br., 79110, Germany

Received 24 January 2001; Revised 20 July 2001; Accepted 24 August 2001.

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Abstract

The phenanthridine alkaloid lycobetaine is a minor constituent of Amaryllidaceae. Inhibition of cell growth was studied in the clonogenic assay on 21 human tumour xenografts (mean IC50 = 0.8 muM). The growth of human leukaemia cell lines was also potently inhibited (mean IC50 = 1.3 muM). Athymic nude mice, carrying s.c. implanted human gastric tumour xenograft GXF251, were treated i.p. with lycobetaine for 4 weeks, resulting in a marked tumour growth delay. Lycobetaine was found to act as a specific topoisomerase IIbeta poison. In the presence of calf thymus DNA, pure recombinant human topoisomerase IIbeta protein was selectively depleted from SDS-gels, whereas no depletion of topoisomerase IIalpha protein was observed. In A431 cells immunoband-depletion of topoisomerase IIbeta was induced, suggesting stabilization of the covalent catalytic DNA-intermediate in living cells. It is reasonable to assume that this mechanism will cause or at least contribute significantly to the antitumour activity. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords:

lycobetaine, ungeremine, topoisomerase IIbeta, cleavable complex, clonogenic assay, gastric carcinoma

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