Aromatase is the enzyme that converts androgen to estrogen.
It is expressed at higher levels in breast cancer tissues than
normal breast tissues. Grape seed extract (GSE) contains
high levels of procyanidin dimers that have been shown in
our laboratory to be potent inhibitors of aromatase. In this
study,GSE was found to inhibit aromatase activity in a dosedependent
manner and reduce androgen-dependent tumor
growth in an aromatase-transfected MCF-7 (MCF-7aro) breast
cancer xenograft model,agree ing with our previous findings.
We have also examined the effect of GSE on aromatase
expression. Reverse transcription-PCR experiments showed
that treatment with 60 Mg/mL of GSE suppressed the levels
of exon I.3–,ex on PII–,and exon I.6–containing aromatase
mRNAs in MCF-7 and SK-BR-3 cells. The levels of exon
I.1–containing mRNA,however ,did not change with GSE
treatment. Transient transfection experiments with luciferasearomatase
promoter I.3/II or I.4 reporter vectors showed the
suppression of the promoter activity in a dose-dependent
manner. The GSE treatment also led to the down-regulation of
two transcription factors,cy clic AMP-responsive element
binding protein-1 (CREB-1) and glucocorticoid receptor
(GR). CREB-1 and GR are known to up-regulate aromatase
gene expression through promoters I.3/II and I.4,respectively.
We believe that these results are exciting in that they show
GSE to be potentially useful in the prevention/treatment of
hormone-dependent breast cancer through the inhibition of
aromatase activity as well as its expression.
(Cancer Res 2006; 66(11): 5960-7)