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* College of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana 71209–0470; and
Palm Oil Research Institute of Malaysia, Kuala Lumpur 50720, Malaysia
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 5-day culture period, treatment with 0–120 µM 
- and 
-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 µM tocotrienol-rich-fraction of palm oil (TRF); 55, 47, and 23 µM 
-tocopherol; 12, 7, and 5 µM -tocotrienol; 8, 5, and 4 µM -tocotrienol; or 7, 4, and 3 µM -tocotrienol in CL-S1, -SA and +SA cells, respectively. Acute 24-hr exposure to 0–250 µM - or -tocopherol (CL-S1, -SA, and +SA) or 0–250 µM -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 µM -tocopherol in -SA and +SA cells, respectively. Additional LD50 doses were determined as the following: 50, 43, and 38 µM TRF; 27, 28, and 23 µM -tocotrienol; 19, 17, and 14 µM -tocotrienol; or 16, 15, or 12 µM -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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