GROWTH-INHIBITORY EFFECTS OF LIPOSOME-ASSOCIATED O-OCTADECYL-2-O-METHYL-SN-GLYCERO-3-PHOSPHOCHOLINE

The growth inhibitory effects of O-ocladecyl-2-O-methyl-sn-glycero-3-p hosphocholine (ET-18-OCH3) and various liposome compositions of ET-18- OCH3 were compared in a standardized growth inhibition assay utilizing a diverse tumor cell line panel including cell lines expressing multi drug resistance. ET-18-OCH3 and ELL-12 (4:3:1:2, lesterol/dioleoylphos phatidylethanolamine-glutaric acid/ET-18-OCH3), an optimal liposomal E T-18-OCH3 formulation, inhibited growth in the micromolar range in dru g-sensitive and -resistant cells. In general, ET-18-OCH3-liposomes wer e about twofold less growth inhibitory than ET-18-OCH3. However, the k nown hemolytic effects of ET-18-OCH3 were greatly reduced, up to 20 or more times, by liposome association. The effects of ET-18-OCH3 and EL L-12 were compared in intracellular [Ca2+] modulation and DNA fragment ation assays. ET-18-OCH3 elicited both concentration-and serum-depende nt transient and permanent increases in intracellular [Ca2+]. In contr ast, ELL-12 did not modulate intracellular [Ca2+]. ET-18-OCH3 and ELL- 12 similarly affected DNA fragmentation, which may be indicative of ap optosis. The results suggest that, although the specific growth inhibi tory effects of ET-18-OCH3 and ELL-12 are similar, associating ET-18-O CH3 with stable well-characterized liposomes eliminates nonspecific ce ll membrane-associated lytic effects.