Tocotrienols inhibit growth of ZR-75-1 breast cancer cells.
The vitamin E component of palm oil provides a rich source of tocotrienols which have been shown previously to be growth inhibitory to two human breast cancer cell lines: responsive MCF7 cells and unresponsive MDA-MB-231 cells. Data presented here shows that the tocotrienol-rich fraction (TRF) of palm oil and individual fractions (alpha, gamma and delta) can also inhibit the growth of another responsive human breast cancer cell line, ZR-75-1. At low concentrations in the absence of oestrogen tocotrienols stimulated growth of the ZR-75-1 cells, but at higher concentrations in the presence as well as in the absence of oestradiol, tocotrienols inhibited cell growth strongly. As for MCF7 cells, alpha-tocopherol had no effect on growth of the ZR-75-1 cells in either the absence or presence of oestradiol. In studying the effects of tocotrienols in combination with antioestrogens, it was found that TRF could further inhibit growth of ZR-75-1 cells in the presence of tamoxifen (10(-7) M and 10(-8) M). Individual tocotrienol fractions (alpha, gamma, delta) could inhibit growth of ZR-75-1 cells in the presence of 10(-8) M oestradiol and 10(-8) M pure antioestrogen ICI 164,384. The immature mouse uterine weight bioassay confirmed that TRF could not exert oestrogen antagonist action in vivo. These results provide evidence of wider growth-inhibitory effects of tocotrienols beyond MCF7 and MDA-MB-231 cells, and with an oestrogen-independent mechanism of action, suggest a possible clinical advantage in combining administration of tocotrienols with antioestrogen therapy.
Palm Oil Research Institute of Malaysia, PO Box 10620, Kuala Lumpur 50720, Malaysia.
K
K
Nesaretnam
S
S
Dorasamy
P D
PD
Darbre
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000502:physiology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014599:Uterus / Q000187:drug effects; D014810:Vitamin E / Q000494:pharmacology / Q000627:therapeutic use*
D000972:Antineoplastic Agents, Phytogenic; D004965:Estrogen Antagonists; D013629:Tamoxifen; D014810:Vitamin E; D004958:Estradiol