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

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.