Erucylphosphocholine, a novel antineoplastic ether lipid, blocks growth and induces apoptosis in brain tumor cell lines in vitro.
A potential benefit of alkylphosphocholines in brain tumor therapy was evaluated. The in vitro effects of the intravenously applicable erucylphosphocholine (ErPC) on proliferation, viability, morphology and cell cycle distribution of a rat glioma, four human astrocytoma/glioblastoma and a human medulloblastoma cell line were analyzed daily after continuous drug-exposure for up to six days. ErPC exerted strong cytostatic and direct cytotoxic effects on all cell lines tested at drug concentrations that are achieved in the rat brain after repeated intravenous injections of nontoxic drug doses. Concentrations of 70 microM (T98G, A172, 85HG66, 86HG39) and 110 microM (C6, D283 Med) led to complete cell death within 48-96 h. Particular characteristics of ErPC action are i) the accumulation of cells with a 4n DNA content corresponding to the G2/M-phase of the cell cycle, ii) the formation of two- and multinucleated cells and iii) the induction of apoptosis.
Jendrossek
V
V
University of Göttingen Medical School, Children's Hospital, 37075 Göttingen, Germany.
Erdlenbruch
B
B
Hunold
A
A
Kugler
W
W
Eibl
H
H
Lakomek
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D010767:Phosphorylcholine; C075010:erucylphosphocholine