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  • Title: Lycobetaine acts as a selective topoisomerase II beta poison and inhibits the growth of human tumour cells.
    Author: Barthelmes HU, Niederberger E, Roth T, Schulte K, Tang WC, Boege F, Fiebig HH, Eisenbrand G, Marko D.
    Journal: Br J Cancer; 2001 Nov 16; 85(10):1585-91. PubMed ID: 11720449.
    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 IC(50) = 0.8 microM). The growth of human leukaemia cell lines was also potently inhibited (mean IC(50) = 1.3 microM). 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 II beta poison. In the presence of calf thymus DNA, pure recombinant human topoisomerase II beta protein was selectively depleted from SDS-gels, whereas no depletion of topoisomerase II alpha protein was observed. In A431 cells immunoband-depletion of topoisomerase II beta 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.
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