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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

A novel nontoxic alkyl-phospholipid with selective antitumor activity, plasmanyl-(N-acyl)-ethanolamine (PNAE), isolated from degenerating chick embryonal tissues and from an anticancer biopreparation cACPL.

A novel alkyl-phospholipid with selective antitumor activity was isolated from an anticancer biopreparation cACPL (crude anticancer phospholipids) and from tissues of degenerating chick embryos. The alkyl-phospholipid was isolated and purified by chromatographic methods using silicic acid column chromatography and thin layer chromatography. The chemical structure of the alkyl-phospholipid was characterized by thin-layer chromatographic analysis of the degradation products after enzymatic digestion with phospholipase C from Bacillus cereus and with phospholipase D, by two-dimensional thin-layer chromatography, infrared spectrum, and mass spectrometric analysis. The alkyl-phospholipid was identified as 1-O-alkyl-2-acyl-sn-glycero-3-phospho-(N-acyl)-ethanolamine, i.e. plasmanyl-(N-acyl)-ethanolamine (PNAE), the main molecular species being 1-O-octadecyl-2-oleoyl-sn-glycero-3-phospho-(N-palmitoyl)-ethanol-amine. PNAE exhibits a selective cytolytic effect on human tumor cells HEp-2, HeLa and T24 in tissue cultures at the concentration of 25 micrograms PNAE per ml and 66-98% inhibition of DNA synthesis in the human tumor cells at concentration as low as 2.5 micrograms/ml, but it does not inhibit at a 50-fold higher concentration the DNA synthesis and normal growth of human fibroblasts (cell line LEP). PNAE represents the main biologically active antitumor component of the cACPL biopreparation and exhibits a significant antitumor effect in vivo in B10/An mice bearing Mc11 fibrosarcoma. Possible molecular mechanism of the selective antitumor activity of PNAE is discussed, involving the selective disturbance of phospholipid metabolism in tumor cells, leading to progressive destruction of tumor cell membranes. The fact that PNAE is nontoxic and selectively active against tumor cells at nanomolar concentrations in vitro as well as in vivo, indicates the possibility of its clinical use. PNAE and cACPL biopreparation might provide a very useful new tool for human anticancer chemotherapy.[1]


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