Anti-tumor activity of synthetic alkyllysophospholipids and glycolipids

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(1) Alkylphospholipids1-0-Octadecyl-2-0-methyl-glycero-3-phosphocholine (ET18-0Me) has been reported to prossess difine anti-tumor effect in vivo. Lysophospholipid analogs were chemically synthesized and their anti-tumor activity against mouse experimental tumor (Sarcoma 180, MM46) were examined. Among them, 1-0-octadecy-2-0-acetoacetyl-glycero-3-phosphocholine was found to show anti-tumor activity similar to ET18-0Me, with less acute toxicity.Intravenous injection of the ET18-0Me with sn-3 configuration retarded the subcutaneous growth of Sarcoma 180 cells effectively, while the growth inhibition by the sn-1 isomer was much less effective. This stereospecificity was similar to that observed in their activities as PAF agonist. The acetoacetyl compound, another PAF aganist, showed similar stereospecific anti-tumor action in vivo. These findings suggest that some alkyl lysophospholipids may activate host cells to a cytostatic stage against tumor cells in vivo through binding to a PAF rec … More eptor. Our preliminary result indicated that the responsible cells under these conditions might primarily be immature macrophages present in the bone-marrow.On the other hand, under some conditions, the in vivo anti-tumor activity of ET18-0Me may be revealed through direct cytotoxicity and/or modulation of host defense system by 'non-specific' mechanisms.(2) GlycolipidsLiposomes composed of chemically synthesized glyceroglycolipids, such as 1,2-dipalmityl-[ <beta> -cellobiosyl-(1'->3)]-glycerol (Cel-DAG), were found to enhance protective immunity against transplatable tumor cells (sarcoma 180) in ICR mice. Peritoneal exudate cells prepared from mice treated in vivo with Cel-DAG showed cytostatic activity in vivo against the mouse leukemia cell line, EL-4. Adherent cells separated from this preparation showed similar activity.The adherent cell fraction alone showed rather weak cytostatic activity when pretreated with the glyceroglycolipids, and full activity was restored by supplementing with the non-adherent cell fraction. The ability of glycolipids to induce tumoricidal effects was affected by cholesterol content: with increasing cholesterol content, the activities decreased. Less