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

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Lipids

Abstract

Studies were conducted to determine the comparative effects of tocopherols and tocotrienols on normal mammary epithelial cell growth and viability. Cells isolated from midpregnant BALB/c mice were grown within collagen gels and maintained on serum-free media. Treatment with 0–120 μM α-and γ-tocopherol had no effect, whereas 12.5–100 m μM tocotrienol-rich fraction of palm oil (TRF), 100–120 μM δ-tocopherol, 50–60 μM α-tocotrienol, and 8–14 μM γ- or δ-tocotrienol significantly inhibited cell growth in a dose-responsive manner. In acute studies, 24-h exposure to 0–250 μM α-, γ-, and δ-tocopherol had no effect, whereas similar treatment with 100–250 μM TRF, 140–250 μM α-, 25–100 μM γ- or δ-tocotrienol significantly reduced cell viability. Growth-inhibitory doses of TRF, δ-tocopherol, and a-, γ-, and δ-tocotrienol were shown to induce apoptosis in these cells, as indicated by DNA fragmentation. Results also showed that mammary epithelial cells more easily or preferentially took up tocotrienols as compared to tocopherols, suggesting that at least part of the reason tocotrienols display greater biopotency than tocopherols is because of greater cellular accumulation. In summary, these findings suggest that the highly biopotent γ- and δ-tocotrienol isoforms may play a physiological role in modulating normal mammary gland growth, function, and remodeling.

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Abbreviations

BSA:

bovine serum albumin

DMEM:

Dulbecco's modified Eagle's medium

EGF:

epidermal growth factor

HPLC:

high-performance liquid chromatography

IC50 :

treatment dose that induces 50% growth inhibition

LD50 :

treatment dose that induces 50% cell death

MTT:

3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide

α-T:

α-tocopherol

γ-T:

γ-tocopherol

δ-T:

δ-tocopherol

α-T:

α-tocotrienol

γ-T3 :

γ-tocotrienol

δ-T3 :

δ-tocotrienol

TGF:

transforming growth factor

TRF:

tocotrienol-rich fraction

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Author information

Authors and Affiliations

  1. Colleges of Pharmacy, University of Louisiana, 71209-0470, Monroe, Louisiana

    Barry S. McIntyre, Karen P. Briski & Paul W. Sylvester

  2. Colleges of Pharmacy, Washington State University, 99164, Pullman, Washington

    Mark A. Tirmenstein & Marc W. Fariss

  3. Colleges of Pharmacy, Palm Oil Research Institute of Malaysia, 50720, Kuala Lumpur, Malaysia

    Abdul Gapor

Authors
  1. Barry S. McIntyre
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  2. Karen P. Briski
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  3. Mark A. Tirmenstein
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  4. Marc W. Fariss
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  5. Abdul Gapor
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  6. Paul W. Sylvester
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Correspondence to Paul W. Sylvester.

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McIntyre, B.S., Briski, K.P., Tirmenstein, M.A. et al. Antiproliferative and apoptotic effects of tocopherols and tocotrienols on normal mouse mammary epithelial cells. Lipids 35, 171–180 (2000). https://doi.org/10.1007/BF02664767

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  • DOI: https://doi.org/10.1007/BF02664767

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