High dietary level of synthetic vitamin E on lipid peroxidation, membrane fatty acid composition and cytotoxicity in breast cancer xenograft and in mouse host tissue.
High dietary level of synthetic vitamin E on lipid peroxidation, membrane fatty acid composition and cytotoxicity in breast cancer xenograft and in mouse host tissue.
复制标题
乳腺癌异种移植物和小鼠宿主组织中的脂质过氧化，膜脂肪酸组成和细胞毒性的合成维生素E的高饮食水平。
DOI：
10.1186/1475-2867-3-3
复制
发表时间：
2003-03-12
影响因子：
5.8
通讯作者：
Hardman, W. Elaine
中科院分区：
文献类型：
--
作者：
Cameron, Ivan L.;Munoz, Jesus;Barnes, Christopher J.;Hardman, W. Elaine
D-α-生育酚是一种天然存在的维生素E，以前并不知道它有抗肿瘤活性。合成维生素E(Se)是一种常用的膳食补充剂，由d-α-生育酚和7种等摩尔立体异构体组成。为了测试补充Se的抗脂质过氧化和抗肿瘤活性，两组荷人乳腺癌Mb231的裸鼠被饲喂AIN-76饲料，一组添加和不添加2000IU/kg的干粮(相当于900mgAll-rac-α-生育酚或Se)。这就提供了每天大约200毫克/公斤体重的摄入量。这些小鼠在饮食干预开始后的2周或6周被处死。在尸检过程中，切除肿瘤和宿主组织进行组织学和生化分析。补硒6周后，肿瘤生长明显减少。硫代巴比妥酸反应物质是脂质过氧化的指示物，在补充Se的小鼠的肿瘤和宿主组织中受到抑制。在硒处理的小鼠中，肿瘤和宿主组织的微粒体膜和线粒体膜的脂肪酸组成比例较少(n-6C18-2)，花生四烯酸(n-6C20-4)的比例较低，但二十二碳六酸(n-3C22-6)较多。补充Se对血细胞计数和肠道组织学无明显影响，但通过心肌细胞空泡和氧化应激指标(Mn-SOD/GPX1 mRNA比值增加)，提供了一些心脏毒性的证据。硒中至少有一种立体异构体具有抗肿瘤活性。合成维生素E似乎优先稳定膜脂肪酸，在酰链上有更多的双键。虽然硒抑制了肿瘤生长和脂质过氧化，但它可能对心脏有副作用。
d-α-tocopherol is a naturally occurring form of vitamin E not previously known to have antitumor activity. Synthetic vitamin E (sE) is a commonly used dietary supplement consisting of a mixture of d-α-tocopherol and 7 equimolar stereoisomers. To test for antilipid peroxidation and for antitumor activity of sE supplementation, two groups of nude mice bearing a MDA-MB 231 human breast cancer tumor were fed an AIN-76 diet, one with and one without an additional 2000 IU/kg dry food (equivalent to 900 mg of all-rac-α-tocopherol or sE). This provided an intake of about 200 mg/kg body weight per day. The mice were killed at either 2 or 6 weeks after the start of dietary intervention. During necropsy, tumor and host tissues were excised for histology and for biochemical analyses. Tumor growth was significantly reduced by 6 weeks of sE supplementation. Thiobarbituric acid reactive substances, an indicator of lipid peroxidation, were suppressed in tumor and in host tissues in sE supplemented mice. In the sE treated mice, the fatty acid composition of microsomal and mitochondrial membranes of tumor and host tissues had proportionately less linoleic acid (n-6 C 18-2), similar levels of arachidonic acid (n-6 C 20-4), but more docosahexanoic acid (n-3 C 22-6). The sE supplementation had no significant effect on blood counts or on intestinal histology but gave some evidence of cardiac toxicity as judged by myocyte vacuoles and by an indicator of oxidative stress (increased ratio of Mn SOD mRNA over GPX1 mRNA). At least one of the stereoisomers in sE has antitumor activity. Synthetic vitamin E appears to preferentially stabilize membrane fatty acids with more double bonds in the acyl chain. Although sE suppressed tumor growth and lipid peroxidation, it may have side-effects in the heart.
登录
查看更多内容
影响因子：
1.9
作者：
Liu, QY;Tan, BKH
通讯作者：
Tan, BKH
影响因子：
4.8
作者：
Neuzil, J;Weber, T;Weber, C
通讯作者：
Weber, C
影响因子：
2.9
作者：
CHOMCZYNSKI, P;SACCHI, N
通讯作者：
SACCHI, N
影响因子：
5.8
作者：
Hardman WE;Munoz J Jr;Cameron IL
通讯作者：
Cameron IL
影响因子：
4.2
作者：
Kline, K;Yu, WP;Sanders, BG
通讯作者：
Sanders, BG