Effects of reduced dietary linoleic acid intake, alone or combined with an algal source of docosahexaenoic acid, on MDA-MB-231 breast cancer cell growth and apoptosis in nude mice

被引:74
作者
Connolly, JM [1 ]
Gilhooly, EM [1 ]
Rose, DP [1 ]
机构
[1] Amer Hlth Fdn, Div Nutr & Endocrinol, Valhalla, NY 10595 USA
来源
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL | 1999年 / 35卷 / 01期
关键词
D O I
10.1207/S1532791444-49
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Diets rich in linoleic acid (LA), an n-6 fatty acid, stimulate the progression of human breast cancer cell solid tumors in athymic nude mice, whereas docosahexaenoic acid (DHA) and eicosapentaenoic acid, long-chain n-3 fatty acids, exert suppressive effects. lit the present study we used a novel source of DHA, in triglyceride form, to determine the effects of feeding low levels of the fatty acid on the growth of MDA-MB-231 cells injected into the thoracic mammary fat pads of female nude mice. Four different isocaloric diets were used, all of which provided 20% (wt/wt) total fat. The control diets contained 8% (20 mice) or 4% (50 mice) LA; the n-3 fatty acid-supplemented groups of 50 mice were fed 4% LA-containing diets plus 2% or 4% DHA. The tumor growth rates were reduced significantly in mice fed the 4% LA compared with the 8% LA diet; the addition of 4% DHA to the 4% LA-containing diet produced a further reduction in tumor growth rare (p less than or equal to 0.003 at and after Week 6). The final tumor weights were also reduced in the DHA-fed mice compared with the 8% LA dietary group (2% DHA, p = 0.02; 4% DHA, p = 0.01) and in the 4% DHA-fed mice compared with the 4% LA control group (p = 0.02); a similar trend for mice fed the lower level of DHA did not achieve statistical significance. Tumor prostaglandin E-2 concentrations were reduced by feeding the lower LA level; further dose-dependent decreases occurred i,t the DHA dietary groups and were accompanied by reduced levels of 12- and 15-hydroxyeicosatetraenoic acids. These changes in eicosanoid biosynthesis may have been responsible for the observed decreases in cell proliferation, indicated by suppressed Ki-67 expression, and increases in apoptotic activity, as reflected in TdT-mediated dUTP nick end labeling immunohistochemical staining.
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页码:44 / 49
页数:6
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