The steroid derivative EM-1913 is a non-estrogenic inhibitor of steroid sulfatase
(STS), an enzyme involved in the biosynthesis of estrogens and androgens. As an approach
to treat estrogen-dependent diseases such as breast cancer, we want to test EM-1913 in an
estrogen-dependent breast cancer tumor model in vivo. Ovariectomized nude mice were inoculated
with estrogen-sensitive human breast cancer MCF-7 cells and stimulated with sulfated
estradiol (E2S), which is transformed into the potent estrogen estradiol by STS. Tumors
generated after 28 days were treated subcutaneously with EM-1913 administered in a mixture of ethanol
(8%) and propylene glycol (92%). The three doses tested (100 µg, 4 mg/kg; 200 µg, 8 mg/kg; 500 µg, 20
mg/kg) blocked tumor growth induced by E2S. No apparent signs of toxicity in animals were observed at the
different doses during the 30-day treatment period and at the end of treatment by measuring the body and
liver weights. On a panel of cancer cell lines, we observed only very low cytotoxicity at high concentrations
(over 10 µM). These in vivo and in vitro results confirm the potential of EM-1913 as an anticancer agent to
treat estrogen-dependent diseases, at least in a xenograft model of breast cancer, but its use can also be extended
to androgen-dependent diseases such as prostate cancer.
Keywords: Cancer, enzyme inhibitor, estrogen, steroid sulfatase, xenograft.
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