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.
Tominaga
T
T
Department of Surgery, Tokyo Metropolitan Komagome Hospital, Japan.
Yoshida
Y
Y
Matsumoto
A
A
Hayashi
K
K
Kosaki
G
G
D000284:Administration, Oral; D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology*; D013629:Tamoxifen / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D017312:Toremifene / Q000008:administration & dosage / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D013629:Tamoxifen; C038345:droloxifene; C064635:TAT 59; D017312:Toremifene; D005472:Fluorouracil