Selective cytostatic activity of hexadecylphosphocholine against tumor-cells invitro leads to the establishment of an invivo screening system for phospholipid analogs.

Hexadecylphosphocholine (HPC, D-18506, INN: Miltefosine) was characterized in a clonogenic micro assay in vitro with respect to its cytotoxicity against a panel of human and murine tumor cell lines and murine bone marrow cultures (GM-CFC). The KB human epithelial carcinoma line was found to be more sensitive by at least one order of magnitude than the murine tumor cell lines which are in vivo insensitive to the drug. Xenotransplants of the KB cell line into nude mice were highly sensitive to HPC with optimal treatment resulting in total regression of the tumor. Twenty-seven structural analogues of HPC were tested in vivo in our normal screening system, the dimethylbenz(a)anthracene(DMBA)-induced mammary carcinoma of the rat, and against KB-xenotransplants. 88 % of the compounds rated identically in both models, no compound was classified falsely negative in the KB model. These results allow to adopt the KB-model, which is easier to perform, as a reliable primary screening system for phospholipid analogues without the risk of missing active compounds.