Effects of tamoxifen and the derivative (TAT) on cell cycle of MCF-7 in vitro.

The growth inhibitory activity and influences on cell-cycle progression of tamoxifen (TAM) and its derivatives [toremifene(NK), droloxifene (FK) and TAT-59 (TAT) against MCF-7, cells, an estrogen respondent human breast cancer cell line were investigated. TAM and its derivatives exhibited a dose-dependent growth inhibitory activity against MCF-7 cells in the order of TAT > FK > TAM > NK at 48 and 120 hours in vitro. 10(-6) M TAT reduced growth of MCF-7 to 25% of that of control after 120 hours incubation in the presence of 10(-8) M estradiol; however, in the case of TAM the growth of MCF-7 was 73%. FACS analysis showed that 82.7% of the cells were accumulated at G0/1 phase after 120 hours incubation with TAT and its accumulative activity was higher than that of TAM. Moreover, when TAT was used in combination with 5-FU, the accumulative effect was significantly increased. Thus it is suggested that TAT or TAT in combination with 5-FU may be a useful adjuvant treatment against breast cancer.