Antiproliferative and apoptotic effects of tocopherols and tocotrienols onnormal mouse mammary epithelial cells

Studies were conducted to determine the comparative effects of tocopherols and tocotrienols on normal mammary epithelial cell growth and viability. Ce lls isolated from midpregnant BALB/c mice were grown within collagen gels a nd maintained on serum-free media. Treatment with 0-120 mu M alpha- and gam ma-tocopherol had no effect, whereas 12.5-100m mu M tocotrienol-rich fracti on of palm oil (TRF), 100-120 mu M delta-tocopherol, 50-60 mu M alpha-tacot rienol, and 8-14 mu M gamma- or delta-tocotrienol significantly inhibited c ell 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 simi lar 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-inhibit ory doses of TRF, delta-tocopherol, and alpha-, gamma-, and delta-tocotrien ol were shown to induce apoptosis in these cells, as indicated by DNA fragm entation. 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 th an tocopherols is because of greater cellular accumulation. In summary, the se findings suggest that the highly biopotent gamma- and delta-tocotrienol isoforms may play a physiological role in modulating normal mammary gland g rowth, function, and remodeling.