Awad A B, Young A L, Fink C S
Nutrition Program, State University of New York at Buffalo 14214, USA.
Cancer Lett. 1996 Nov 12;108(1):25-33. doi: 10.1016/s0304-3835(96)04382-0.
The objective of the present study was to investigate the effect of membrane fatty acid (FA) composition on the activity of phospholipase C (PLC) in HT-29 human colon cancer cells. The membrane FA composition was altered by supplementing cultured cells with FAs of different composition. The FAs were stearic acid (18:0; SA), gamma linolenic acid (18:3 omega 6; gamma LnA); alpha linolenic acid (18:3 omega 3; alpha LnA;); eicosapentaenoic acid (20:5 omega 3; EPA) and docosahexaenoic acid (22:6 omega 3; DHA). The fatty acids were supplemented as a FA/BSA complex. Cells supplemented with SA served as the control. Tumor growth was followed by counting the number of cells in culture. The results indicate that polyunsaturated fatty acid (PUFA) supplementation had no consistent effect on tumor growth from 1 day to another throughout the 15 days of growth. The fatty acid composition of membranes indicates that cells incorporated and modified the supplemented fatty acids by desaturation, elongation and retroconversion. The unsaturation index (UI) of membranes of cells supplemented with EPA and DHA was higher than other groups. PLC activity; measured in the absence of GTP gamma(S) in the assay mixture; was not influenced by membrane FA modification. However, in the presence of GTP gamma(S) PLC of cells supplemented with 18:3(omega 6) was the lowest among the groups. It has been shown that 18:3(omega 6) accumulated the most in the phosphatidylethanolamine (PE) fraction. There was a negative correlation between the activity of PLC in the presence of G protein activation and PE 18:3 (omega 6) content without affecting UI. It was concluded that G protein may be sensitive to the level of 18:3(omega 6) content and not to the general fluidity of the membranes.
本研究的目的是调查膜脂肪酸(FA)组成对HT-29人结肠癌细胞中磷脂酶C(PLC)活性的影响。通过用不同组成的脂肪酸补充培养细胞来改变膜脂肪酸组成。这些脂肪酸分别是硬脂酸(18:0;SA)、γ-亚麻酸(18:3 ω6;γLnA)、α-亚麻酸(18:3 ω3;αLnA)、二十碳五烯酸(20:5 ω3;EPA)和二十二碳六烯酸(22:6 ω3;DHA)。脂肪酸以FA/牛血清白蛋白(BSA)复合物的形式补充。补充SA的细胞作为对照。通过计数培养物中的细胞数量来跟踪肿瘤生长。结果表明,在整个15天的生长过程中,补充多不饱和脂肪酸(PUFA)对肿瘤生长从一天到另一天没有一致的影响。膜的脂肪酸组成表明细胞通过去饱和、延长和逆转化作用掺入并修饰了补充的脂肪酸。补充EPA和DHA的细胞的膜不饱和指数(UI)高于其他组。在测定混合物中不存在GTPγ(S)的情况下测量的PLC活性不受膜脂肪酸修饰的影响。然而,在存在GTPγ(S)的情况下,补充18:3(ω6)的细胞的PLC在各组中是最低的。已经表明18:3(ω6)在磷脂酰乙醇胺(PE)部分中积累最多。在存在G蛋白激活的情况下PLC的活性与PE 18:3(ω6)含量之间存在负相关,而不影响UI。得出的结论是,G蛋白可能对18:3(ω6)含量水平敏感,而不是对膜的一般流动性敏感。