Anti-neoplastic action of peritoneal macrophages following oral administration of ether analogues of lysophospholipids.
Inflamed lesions of normal and cancerous tissues induce activation of phospholipase A in plasma membranes resulting in the release of various decomposed products of membranous lipids. Oral administration in mice of dodecylglycerol (DDG), a synthetic alkyglycerol, and an alkyl ether analogue of lysophospholipids, 1-0-octadecyl-2-0-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3-choline) efficiently activated peritoneal macrophages for enhanced Fc-mediated (fragment crystallisable) ingestion of red blood cells and direct cytotoxic action on retinoblastoma tumour cells. The activated macrophages not only inhibited tumour cell growth, but also markedly induced cytolysis of tumour cells. The antitumour capability of the macrophages was substantiated by luminol-enhanced chemiluminescence. These findings suggest that dodecylglycerol and ET-18-OCH3-choline administered orally retain their ability to induce a high level of macrophage activation and tumour cytotoxicity, just as occurs with intraperitoneal administration. Thus, these compounds have potential practical application in chemotherapy and immunotherapy of the tumour, which could be accomplished by simple oral rather than parenteral administration.
Ngwenya
B Z
BZ
Department of Microbiology and Immunology, Hahnemann University, Philadelphia, Pennsylvania 19102-1192.
Fiavey
N P
NP
Mogashoa
M M
MM
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D005134:Eye Neoplasms / Q000473:pathology; D005989:Glycerides / Q000494:pharmacology*; D007700:Kinetics; D007848:Laurates / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D050178:Monoglycerides; D010529:Peritoneal Cavity / Q000166:cytology; D010587:Phagocytosis / Q000187:drug effects; D010742:Phospholipid Ethers / Q000494:pharmacology*; D012175:Retinoblastoma / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D005989:Glycerides; D007848:Laurates; D050178:Monoglycerides; D010742:Phospholipid Ethers; C026659:edelfosine; C020777:monolaurin