New tumoricidal semisynthetic ether phospholipid, plasmanyl-(N-acyl)ethanolamine (PNAE(s)) and enhancement of its tumoricidal activity by calcium ions.
Recently we described a novel, nontoxic, natural ether phospholipid with selective antitumor activity, 1-0-alkyl-2-acyl-sn-glycero-3-phospho-(N-acyl)ethanolamine, i.e., plasmanyl-(N-acyl)ethanolamine (PNAE), isolated from ischemic tissue of chick embryo. The chemical structure of PNAE has been confirmed by partial synthesis. The semisynthetic preparation PNAE(s), 1-0-octadecyl-2-oleoyl-sn-glycero-3-phospho-(N-palmitoyl)ethanolamine, exhibited tumoricidal activity against human tumor cells T24 and mouse sarcoma cells Mcll as well as in vivo against murine sarcomas S-180 and Mcll. PNAE(s) selectively destroyed tumor cell membranes as has been demonstrated by scanning electron microscopy. The antitumor activity of PNAE(s) in vitro and in vivo was significantly enhanced by Ca2+ ions. These results may be explained by selective damage of tumor cell membranes by PNAE(s), increasing also the tumor cell membrane permeability for exogenous Ca2+ ions and altering the intracellular calcium homeostasis in tumor cells. By increased concentration of Ca2+ in tumor cell cytosol selective damage and lysis of tumor cells was induced. The combined use of parenteral administration of PNAE(s) and peroral doses of calcium gluconate may provide a new approach to enhancement of antitumor activity of PNAE(s) by Ca2+ in a very selective and nontoxic antitumor therapy.
Kára
J
J
Laboratory of Envolutionary Biology, Czech Academy of Sciences, Prague.
Konovalova
A L
AL
Krasnova
M A
MA
Liebl
V
V
Bejsovcová
L
L
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity*; D002118:Calcium / Q000627:therapeutic use / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005354:Fibrosarcoma / Q000188:drug therapy; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010714:Phosphatidylethanolamines / Q000627:therapeutic use* / Q000633:toxicity*; D012510:Sarcoma 180 / Q000188:drug therapy; D012513:Sarcoma, Experimental / Q000188:drug therapy*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D010714:Phosphatidylethanolamines; C078193:1-O-octadecyl-2-oleoyl-sn-glycero-3-phospho-(N-palmitoyl)ethanolamine; D002118:Calcium; D013936:Thymidine