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

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 mu M alpha- and gamma-tocopherol had no effect, whereas 12.5-100m mu M tocotrienol-rich fraction of palm oil (TRF), 100-120 mu M delta-tocopherol, 50-60 mu M alpha-tacotrienol, and 8-14 mu M gamma- or delta-tocotrienol significantly inhibited cell growth in a dose-responsive manner. In acute studies, 24-h exposure to 0-250 mu M alpha-, gamma-, and delta-tocopherol had no effect, whereas similar treatment with 100-250 mu M TRF, 140-250 mu M alpha-, 25-100 mu M gamma- or delta-tocotrienol significantly reduced cell viability. Growth-inhibitory doses of TRF, delta-tocopherol, and alpha-, gamma-, and delta-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 gamma- and delta-tocotrienol isoforms may play a physiological role in modulating normal mammary gland growth, function, and remodeling.