Cytotoxic effects of hexadecylphosphocholine in neoplastic cell lines including drug-resistant sublines in vitro

Hexadecylphosphocholine (HPC) was tested in comparison with the membrane-toxic reference ether lipid ET-18-OCH3 for cytotoxic (trypan blue dye exclusion) and cytostatic/antiproliferative [( 3H]thymidine uptake) activity in six cell lines of human hematologic malignancies, six cell lines of human solid tumors and four drug-resistant sublines and their respective non-resistant parent lines in vitro. HPC showed time- and dose-dependent antiproliferative and cytotoxic activity in almost all cell lines, including drug-resistant sublines over a dose range of 2-120 microM and after incubation times of 24, 48 and 72 h. However, ET-18-OCH3 showed a significantly higher activity than HPC, when both compounds were compared on an equimolar basis. The human tumor clonogenic assay confirmed these results. Furthermore, no cross-resistance for HPC with colchicine or methotrexate and partial cross-resistance for HPC with adriamycin was found in cell lines selected for drug resistance. In conclusion, HPC is cytotoxic for neoplastic cells of different histologies including drug-resistant sublines in vitro. Although its cytotoxicity starts at somewhat higher doses when compared to ET-18-OCH3, further testing as an experimental anticancer drug in vivo and comparative cytotoxicity studies with hematopoietic progenitor cells from bone marrow are recommended.