The proliferation of MCF-7, human
breast cancer cell line, was stimulated by
testosterone and
estradiol. The
aromatase activity in MCF-7 cells, which catalysed the conversion of
testosterone to
estradiol, was inhibited by a novel non-steroidal
aromatase inhibitor, YM5111, with the IC50 of 0.2 nM, indicating that its inhibitory activity was 5.5 times more potent than that of
CGS 16949A.
YM511 inhibited the proliferation of MCF-7 stimulated by
testosterone but did not inhibit the cell proliferation stimulated by
estradiol. The IC50 values of
YM511 for cell growth and
DNA synthesis were 0.13 nM and 0.18 nM, respectively, demonstrating that
YM511 was about 3-5 times more potent than
CGS 16949A and had no anti-estrogenic or cytotoxic activity.
YM511 significantly inhibited
testosterone-stimulated transcriptional activation of
estrogen-responsive
element (ERE) in MCF-7 cells transfected transiently with ERE-
luciferase reporter plasmid. The IC50 of
YM511 for transactivation was 0.36 nM, suggesting that its inhibitory potency was comparable to the inhibition of
aromatase activity of MCF-7 cells. These data may indicate that the inhibition by
YM511 of cell proliferation of MCF-7 is attributed to the decreased production of
estrogen due to the inhibition of
aromatase activity.
YM511 may be useful in the treatment of
estrogen-dependent
cancers.