Growth inhibitory effects of liposome-associated 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphocholine

被引：16

作者：

Peters, AC ^{[1
]}

Ahmad, I ^{[1
]}

Janoff, AS ^{[1
]}

Pushkareva, MY ^{[1
]}

Mayhew, E ^{[1
]}

机构：

[1] LIPOSOME CO INC,PRINCETON,NJ 08540

来源：

LIPIDS | 1997年 / 32卷 / 10期

关键词：

D O I：

10.1007/s11745-997-0135-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The growth inhibitory effects of 1-O-ocladecyl-2-O-methyl-sn-glycero-3-phosphocholine (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 multidrug resistance. ET-18-OCH3 and ELL-12 (4:3:1:2, dioleoylphosphatidylcholine/cholesterol/dioleoylphosphatidylethanolamine-glutaric acid/ET-18-OCH3), an optimal liposomal ET-18-OCH3 formulation, inhibited growth in the micromolar range in drug-sensitive and -resistant cells. In general, ET-18-OCH3-liposomes were about twofold less growth inhibitory than ET-18-OCH3. However, the known 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 ELL-12 were compared in intracellular [Ca2+] modulation and DNA fragmentation assays. ET-18-OCH3 elicited both concentration-and serum-dependent transient and permanent increases in intracellular [Ca2+]. In contrast, ELL-12 did not modulate intracellular [Ca2+]. ET-18-OCH3 and ELL-12 similarly affected DNA fragmentation, which may be indicative of apoptosis. The results suggest that, although the specific growth inhibitory effects of ET-18-OCH3 and ELL-12 are similar, associating ET-18-OCH3 with stable well-characterized liposomes eliminates nonspecific cell membrane-associated lytic effects.

引用

页码：1045 / 1054

页数：10

共 35 条

[1]

Ahmad I, 1997, CANCER RES, V57, P1915

[2]

BERGMANN J, 1994, ANTICANCER RES, V14, P1549

[3] INOSITOL TRISPHOSPHATE AND CALCIUM SIGNALING [J].