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  • Title: Glycosylated antitumor ether lipids are more effective against oncogene-transformed fibroblasts than alkyllysophospholipids.
    Author: Samadder P, Byun HS, Bittman R, Arthur G.
    Journal: Anticancer Res; 1998; 18(1A):465-70. PubMed ID: 9568121.
    Abstract:
    We have investigated the antiproliferative effects of different types of antitumor ether lipids (AELs) against non-transformed and transformed fibroblasts. The compounds examined were choline phosphate-containing alkyllysophospholipids (1-O-octadecyl-2-O-methyl glycerophosphocholine (ET18-OCH3), 2'-(trimethylammonio)ethyl 3-(hexadecyloxy)-2-(methoxymethyl)propylphosphate (oxo-BM 41.440), 2'-(triethylammonio)ethyl 4-(hexadecyloxy)-3-methoxybutane phosphonate (ET16-OCH3-phosphonocholine)), and glycosylated ether-linked diglycerides (1-O-hexadecyl-2-O-methyl-3-S-(beta-D-1'-thioglucopyranosyl-sn-gly cerol) [ET16-OCH3-beta-thio-Glc] and 1-O-hexadecyl-2-O-methyl-3-O-(2'amino-2'-deoxy-beta-D-glucopyranosyl)-sn -glycerol (ET16-OCH3-Gln)). The choline phosphate-containing alkyllysophospholipids (ALPs) had little or moderate effect on the proliferation and none on the viability of NIH 3T3 clone 7, and sublines transformed by raf (NIH/9IV #5), fes (Fes 1), src (Src 1) and mos (Mos 1) oncogenes. The glycosylated ether-linked diglycerides were more effective than the choline phosphate-containing ALPs. Of the two ether-linked diglycerides, ET16-OCH3-beta-thio-Glc did not affect the viability of the cells at any of the concentrations examined while ET16-OCH3-Gln was cytotoxic to all the transformed cell lines at concentrations equal to or greater than 9 microM. The IC50 for ET16-OCH3-Gln was 6.4 microM for Mos 1, 6.5 microM for NIH/9IV #5, 7.5 microM for Src 1, 8.2 microM for Fes 1 and 8.4 microM for NIH 3T3 clone 7. These results suggest that the ether-linked diglycerides may be more effective against fibrosarcomas than the cholinephosphate containing ALPs. Also, with the exception of ET16-OCH3-Gln there was no significant difference in the effect of the compounds on the transformed and untransformed cell lines, suggesting that the selectivity displayed by AELs may depend on both the type of compound and transformation in the cell.
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