A new triphenylethylene compound, Fc-1157a

Abstract

The antitumor effects of a new antiestrogen, Fc-1157a have been studied in vitro and in vivo. In vitro the effect of Fc-1157a was comparable to that of tamoxifen. The effect was dose-dependent, and at concentrations higher than 10(-6) mol/1 Fc-1157a induced real cell death of the MCF-7 cells. In DMBA-induced mammary cancer in rats Fc-1157a decreased the number of new tumors and inhibited the growth of existing tumors, these effects being statistically highly significant. The ratio of growing tumors to stable and regressing tumors was significantly decreased. Although these effects were slightly stronger with Fc-1157a than with tamoxifen, the difference between these two compounds was not statistically significant. Murine uterine sarcoma, an estrogen receptor-negative tumor, was resistant to tamoxifen, but was statistically significantly inhibited by high doses (100 and 200 mg/kg-1 day-1 for 5 days) of Fc-1157a. The antitumor effects of Fc-1157a are due mainly to the antiestrogenic activity. At high concentrations in vitro and at high doses in vivo Fc-1157a exerts antitumor effects some of which are different from those of tamoxifen and are directed even against estrogen receptor-negative tumors. The exact mechanism of the observed cytolytic effect at high doses is unknown.

Tamoxifen blocks chloride channels. A possible mechanism for cataract formation.

“…4-Hydroxy-tamoxifen, a metabolite of tamoxifen generated in vivo, inhibited the chloride currents in S1/1.1 cells slightly less than tamoxifen (65±13% [n = 3] and 88±8% [n = 5] inhibition after 1 min at 5 and 10 ,M 4-OH tamoxifen, respectively). The related antiestrogen, toremifene (27), as well as its 4-hydroxy metabolite, at 5 tzM, each inhibited the chloride currents (in NIH3T3 MDR] cells) by 75±2% (n = 7) and 74±7% (n = 4), respectively (means±SEM).…”

The Efficacy of Tamoxifen in Estrogen Receptor–Positive Breast Cancer Cells Is Enhanced by a Medical Nutriment

“…1 Tamoxifen has both a pro-and antiestrogenic effect on the nuclear estrogen receptors (ER), modifies the function of the plasma membrane, the microsomes, the proliferative and antiproliferative factors as TGF or cyclins, et cetera. [2][3][4][5] As a "selective ER modulator" (SERM), 6 tamoxifen significantly influences the activity of ER.…”

Cyclophosphamide, Adriamycin, 5-Fluorouracil and High-dose Toremifene for Patients with Advanced/Recurrent Breast Cancer

“…(6,7). TOR has been observed to be more effective than TAM with milder toxicity at high doses in certain animal tumor models (8,9).…”