Document Detail

Antiproliferative and apoptotic effects of tocopherols and tocotrienols on preneoplastic and neoplastic mouse mammary epithelial cells.
MedLine Citation:
PMID:  10964265     Owner:  NLM     Status:  MEDLINE    
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 microM 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 microM tocotrienol-rich-fraction of palm oil (TRF); 55, 47, and 23 microM delta-tocopherol; 12, 7, and 5 microM alpha-tocotrienol; 8, 5, and 4 microM gamma-tocotrienol; or 7, 4, and 3 microM delta-tocotrienol in CL-S1, -SA and +SA cells, respectively. Acute 24-hr exposure to 0-250 microM alpha- or gamma-tocopherol (CL-S1, -SA, and +SA) or 0-250 microM 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 microM delta-tocopherol in -SA and +SA cells, respectively. Additional LD50 doses were determined as the following: 50, 43, and 38 microM TRF; 27, 28, and 23 microM alpha-tocotrienol; 19, 17, and 14 microM gamma-tocotrienol; or 16, 15, or 12 microM 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.
B S McIntyre; K P Briski; A Gapor; P W Sylvester
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)     Volume:  224     ISSN:  0037-9727     ISO Abbreviation:  Proc. Soc. Exp. Biol. Med.     Publication Date:  2000 Sep 
Date Detail:
Created Date:  2000-09-19     Completed Date:  2000-09-19     Revised Date:  2007-11-02    
Medline Journal Info:
Nlm Unique ID:  7505892     Medline TA:  Proc Soc Exp Biol Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  292-301     Citation Subset:  IM    
College of Pharmacy, University of Louisiana at Monroe, Monroe, Louisiana 71209-0470, USA.
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MeSH Terms
Antineoplastic Agents / pharmacology*,  therapeutic use
Apoptosis / drug effects*
Cell Division / drug effects
Cell Survival / drug effects
Cell Transformation, Neoplastic / drug effects,  pathology
DNA Fragmentation / drug effects
Dose-Response Relationship, Drug
Epithelial Cells / drug effects,  pathology
Mammary Neoplasms, Animal / drug therapy,  pathology*
Neoplasm Invasiveness / pathology
Precancerous Conditions / drug therapy,  pathology*
Time Factors
Tumor Cells, Cultured
Vitamin E / analogs & derivatives*,  chemistry,  pharmacology*,  therapeutic use
Reg. No./Substance:
0/Antineoplastic Agents; 1406-18-4/Vitamin E

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