FC1271a is a novel
triphenylethylene compound with a tissue-selective profile of
estrogen agonistic and weak antagonistic effects. It specifically binds to the
estrogen receptor alpha and beta with affinity closely similar to that of
toremifene and
tamoxifen. To study the in vivo effects of the compound, 4-month-old rats were
sham operated (
sham) or ovariectomized (OVX) and treated daily for 4 weeks with various doses of FC1271a or vehicle (orally). FC1271a was able to oppose OVX-induced bone loss by maintaining the trabecular bone volume of the distal femur. Accordingly, the OVX-induced loss of bone strength was prevented at doses of 1 and 10 mg/kg. FC1271a also prevented the OVX-induced increase in serum
cholesterol in a dose-dependent manner. No significant changes in uterine wet weight or morphology were observed in the OVX-rats treated with 0.1 or 1 mg/kg FC1271a, but at a dose of 10 mg/kg it had a slightly
estrogenic effect. In immature rats the effect of FC1271a on uterine wet weight was less stimulatory than that of
toremifene or
tamoxifen, but more stimulatory than that of
raloxifene or
droloxifene. The appearance of the dimethylbenzanthracene (DMBA)-induced mammary
tumors was inhibited by treatment of DMBA-treated rats with FC1271a in a dose-dependent manner. In human MCF-7
breast cancer cell
tumors raised in nude mice in the presence of
estrogen, the growth and expression of pS2 marker gene could not be maintained after
estrogen withdrawal by treatment with FC1271a. No formation of
DNA adducts was observed in the liver of the FC1271a-treated rats. In conclusion, the bone-sparing, antitumor, and
cholesterol-lowering effects of FC1271a combined with a low uterotropic activity and lack of liver toxicity indicate that FC1271a could be an important alternative in planning antiosteoporosis
therapy for
estrogen deficiency.