Lariciresinol is a dietary
lignan that accounts for a significant portion of the total
phytoestrogen intake from Western foods. Recent epidemiological studies suggest that high dietary intake of
lignans and
lariciresinol is associated with reduced
breast cancer risk. However, no causal relationship between
lariciresinol intake and
breast cancer development has been established. In this study, we investigated for the first time the effects and possible mechanisms of action of
lariciresinol on
hormone responsive
mammary cancer in vivo in dimethylbenz[a]
anthracene induced
mammary cancer in rats, and in human MCF-7
breast cancer xenografts in athymic mice. For
tumor bearing rats,
lariciresinol (3 or 15 mg/kg of
body weight) or vehicle was administered p.o. daily for 9 weeks. For E2-maintained ovariectomized athymic mice bearing orthotopic MCF-7
tumors, control diet (AIN-93G) or
lariciresinol containing diet (AIN-93G supplemented with 20 or 100 mg of
lariciresinol/kg of diet) was administered for 5 weeks. In both models,
lariciresinol administration inhibited the
tumor growth and
tumor angiogenesis. In MCF-7 cells,
enterolactone significantly inhibited the E2-stimulated
VEGF secretion. Moreover, in MCF-7 xenografts,
lariciresinol administration enhanced
tumor cell apoptosis and increased
estrogen receptor beta expression.
Lariciresinol and its further metabolites
secoisolariciresinol,
enterodiol and
enterolactone were found in serum of both rats and athymic mice confirming a similar
lignan metabolism pattern as in humans. These findings indicate conceivable importance of dietary
lignan lariciresinol in inhibition of
breast cancer development.