LYSOPHOSPHATIDYLCHOLINE ATTENUATES THE CYTOTOXIC EFFECTS OF THE ANTINEOPLASTIC PHOSPHOLIPID 1-O-OCTADECYL-2-O-METHYL-RAC-GLYCERO-3-PHOSPHOCHOLINE

A colony-stimulating factor 1-dependent cell line was used to determine the relationship between the inhibition of phospholipid synthesis and the cytotoxic activity of the antineoplastic ether lipid, 1-O-octadecyl-2-O- methyl-rac-glycero-3-phosphocholine (ET-18-OCH3), ET-18-OCH3 inhibited choline incorporation into phosphatidylcholine as well as total phospholipid synthesis, Exposure to ET-18-OCH3 at the G(1)/S boundary led to the accumulation of cells in G(2), whereas the addition of ET-18-OCH3 in the G(1) phase of the cell cycle prevented entry into the S phase. In both cases, ET-18-OCH, treatment triggered DNA fragmentation and morphological changes associated with apoptosis within 10 h, The addition of lysophosphatidylcholine provided an exogenous source of cellular phospholipid and prevented ET-18-OCH3-dependent accumulation of cells in G(2) and apoptosis, However, lysophosphatidylcholine did not overcome the ET-18-OCH3-dependent G(1) block, although the growth-arrested cells remained viable, These data indicate that restoring phosphatidylcholine synthesis by supplementation with lysophosphatidylcholine over rides the cytotoxic but not the cytostatic activity of ET-18-OCH3.