Antiproliferative and apoptotic effects of tocopherols and tocotrienols on preneoplastic and neoplastic mouse mammary epithelial cells

被引:214
作者
McIntyre, BS
Briski, KP
Gapor, A
Sylvester, PW [1 ]
机构
[1] Univ Louisana, Coll Pharm, Monroe, LA 71209 USA
[2] Palm Oil Res Inst Malaysia, Kuala Lumpur 50720, Malaysia
来源
PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE | 2000年 / 224卷 / 04期
关键词
D O I
10.1046/j.1525-1373.2000.22434.x
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Studies were conducted to determine the comparative effects of tocopherols and tocotrienols on preneoplastic (CL-S1), neoplastic (-SA), and highly malignant (+SA) mouse mammary epithelial cell growth and viability in vitro. Over a B-day culture period, treatment with 0-120 mu M alpha- and gamma-tocopherol had no effect on cell proliferation, whereas growth was inhibited 50% (IC50) as compared with controls by treatment with the following: 13, 7, and 6 mu M tocotrienol-rich-fraction of palm oil (TRF); 55, 47, and 23 mu M delta-tocopherol; 12, 7, and 5 mu M alpha-tocotrienol; 8, 5, and 4 mu M gamma-tocotrienol; or 7, 4, and 3 mu M delta-tocotrienol in CL-S1, -SA and +SA cells, respectively. Acute 24-hr exposure to 0-250 mu M alpha- or gamma-tocopherol (CL-S1, -SA, and +SA) or 0-250 mu M delta-tocopherol (CL-S1) had no effect on cell viability, whereas cell viability was reduced 50% (LD50) as compared with controls by treatment with 166 or 125 mu M delta-tocopherol in -SA and +SA cells, respectively. Additional LD50 doses were determined as the following: 50, 43, and 38 mu MTRF; 27, 28, and 23 mu M alpha-tocotrienol; 19, 17, and 14 mu M gamma-tocotrienol; or 16, 15, or 12 mu M delta-tocotrienol in CL-S1, -SA, and +SA cells, respectively. Treatment-induced cell death resulted from activation of apoptosis, as indicated by DNA fragmentation. Results also showed that CL-S1, -SA, and +SA cells preferentially accumulate tocotrienols as compared with tocopherols, and this may partially explain why tocotrienols display greater biopotency than tocopherols. These data also showed that highly malignant +SA cells were the most sensitive, whereas the preneoplastic CL-S1 cells were the least sensitive to the antiproliferative and apoptotic effects of tocotrienols, and suggest that tocotrienols may have potential health benefits in preventing and/or reducing the risk of breast cancer in women.
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页码:292 / 301
页数:10
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