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 G1/S boundary led to the accumulation of cells in G2, whereas the addition of ET-18-OCH3 in the G1 phase of the cell cycle prevented entry into the S phase. In both cases, ET-18-OCH3 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 G2 and apoptosis. However, lysophosphatidylcholine did not overcome the ET-18-OCH3-dependent G1 block, although the growth-arrested cells remained viable. These data indicate that restoring phosphatidylcholine synthesis by supplementation with lysophosphatidylcholine overrides the cytotoxic but not the cytostatic activity of ET-18-OCH3.
Boggs
K P
KP
Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38101, USA.
Rock
C O
CO
Jackowski
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D007700:Kinetics; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D010742:Phospholipid Ethers / Q000037:antagonists & inhibitors / Q000633:toxicity*; D013539:Simian virus 40 / Q000235:genetics; D013997:Time Factors; D014162:Transfection
D000970:Antineoplastic Agents; D008244:Lysophosphatidylcholines; D010742:Phospholipid Ethers; C026659:edelfosine