Donald Poirier, Jenny Roy, Rene Maltais and Diana Ayan Pages 65 - 73 ( 9 )
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.
Cancer, enzyme inhibitor, estrogen, steroid sulfatase, xenograft.
Laboratory of Medicinal Chemistry, CHU de Quebec - Research Center (CHUL, T4- 42), 2705 Laurier Boulevard, Quebec (Quebec), G1V 4G2, Canada.