INHIBITION OF PROLIFERATION OF ESTROGEN RECEPTOR-NEGATIVE MDA-MB-435 AND RECEPTOR-POSITIVE MCF-7 HUMAN BREAST-CANCER CELLS BY PALM OIL TOCOTRIENOLS AND TAMOXIFEN, ALONE AND IN COMBINATION
N. Guthrie et al., INHIBITION OF PROLIFERATION OF ESTROGEN RECEPTOR-NEGATIVE MDA-MB-435 AND RECEPTOR-POSITIVE MCF-7 HUMAN BREAST-CANCER CELLS BY PALM OIL TOCOTRIENOLS AND TAMOXIFEN, ALONE AND IN COMBINATION, The Journal of nutrition, 127(3), 1997, pp. 544-548
Tocotrienols are a form of vitamin E, having an unsaturated isoprenoid
side-chain rather than the saturated side-chain of tocopherols. The t
ocotrienol-rich fraction (TRF) from palm oil coritains alpha-tocophero
l and a mixture of alpha-, gamma- and delta-tocotrienols. Earlier stud
ies have shown that tocotrienols display anticancer activity. We previ
ously reported that TRF, alpha-, gamma- and delta-tocotrienols inhibit
ed proliferation of estrogen receptor-negative MDA-MB-435 human breast
cancer cells with 50% inhibitory concentrations (IC50) of 180, 90, 30
and 90 mu g/mL, respectively, whereas alpha-tocopherol had no effect
at concentrations up to 500 mu g/mL. Further experiments with estrogen
receptor-positive MCF-7 cells showed that tocotrienols also inhibited
their proliferation, as measured by [H-3] thymidine incorporation. Th
e IC(50)s for TRF, alpha-tocopherol, alpha-, gamma- and delta-tocotrie
nols were 4, 125, 6, 2 and 2 mu g/mL, respectively. Tamoxifen, a widel
y used synthetic antiestrogen inhibits the growth of MCF-7 cells with
an IC50 of 0.04 mu g/mL. We tested 1:1 combinations of TRF, alpha-toco
pherol and the individual tocotrienols with tamoxifen in both cell lin
es. In the MDA-MB-435 cells, all of the combinations were found to be
synergistic. In the MCF-7 cells, only 1:1 combinations of gamma- or de
lta-tocotrienol with tamoxifen showed a synergistic inhibitory effect
on the proliferative rate and growth of the cells. The inhibition by t
ocotrienols was not overcome by addition of excess estradiol to the me
dium. These results suggest that tocotrienols are effective inhibitors
of both estrogen receptor-negative and -positive cells and that combi
nations with tamoxifen should be considered as a possible improvement
in breast cancer therapy.