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.
Danhauser-Riedl
S
S
Department of Medicine I, Technische Universität, Munich, F.R.G.
Himmelmann
A
A
Steinhauser
G
G
Busch
R
R
Vogler
W R
WR
Rastetter
J
J
Berdel
W E
WE
D000970:Antineoplastic Agents / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004351:Drug Resistance; D006801:Humans; D010742:Phospholipid Ethers / Q000494:pharmacology; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014410:Tumor Stem Cell Assay
D000970:Antineoplastic Agents; D010742:Phospholipid Ethers; D010767:Phosphorylcholine; C026659:edelfosine; C039128:miltefosine