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  • Title: Lack of correlation between cytotoxicity of agonists and antagonists of platelet activating factor [paf-acether] in neoplastic cells and modulation of [3H]-paf-acether binding to platelets from humans in vitro.
    Author: Berdel WE, Korth R, Reichert A, Houlihan WJ, Bicker U, Nomura H, Vogler WR, Benveniste J, Rastetter J.
    Journal: Anticancer Res; 1987; 7(6):1181-7. PubMed ID: 3442414.
    Abstract:
    The 3 ether-lipids ET-18-OCH3, SRI 63-154 and paf-acether, the TLP BM 41.440, the ester-linked 2-LPC and CV-3988, were tested for cytostatic/antiproliferative [3H]-thymidine uptake) and cytotoxic (trypan blue dye exclusion, HTCA) activity in 11 neoplastic human cell lines (U 698-M, Nall-1, Su-DHL-4, RPMI 8226, K 562-4, Li-A, HTB-47, HTB-38, CCL218, 85 HG-59, 85 HG-63) and 1 ALL in vitro. 2-LPC and paf-acether showed either no, or only minor, CV-3988 varying activity. There were no significant differences in the activity of ET-18-OCH3, SRI63-154 and BM 41.440, which showed IC50- and LC50-values of less than or equal to 10 micrograms/ml after incubation periods greater than or equal to 48 hours with or during continuous exposure to the cells. The latter three compounds were then tested for interaction with [3H]-paf-acether binding to intact human platelets: ET-18-OCH3 and SRI63-154 reduced [3H]-paf-acether binding in a time-dependent manner. BM 41.440 did not show this interaction. Thus, since the in vitro cytotoxicity of these lipids did not correlate with their modulation of [3H]-paf-acether binding to human platelets, it was concluded that cytotoxicity of ether-lipids is not mediated by specific paf-acether binding sites similar to those present on human platelets. This finding is important for the future design of antineoplastic lipids.
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