TAT-59, a new triphenylethylene derivative with antitumor activity against hormone-dependent tumors

Toshiyuki Toko, Yoshikazu Sugimoto, Ken Ichi Matsuo, Ryouko Yamasaki, Setsuo Takeda, Konstanty Wierzba, Tetsuji Asao, Yuji Yamada

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

The antiestrogenic action of TAT-59 {(E)-4-[1-[4-[2-(dimethylamino)ethoxy]-phenyl]-2-(4-isopropyl)phenyl-1-butenyl] phenyl monophosphate} was characterized and compared with that of Tamoxifen (TAM). Its active metabolite, 4-OH-TAT-59, had a high binding affinity to estrogen receptor (ER), present in the cytosol of the uterus of immature rat, similar to estradiol. TAT-59 and 4-OH-TAT-59 inhibited in vitro estrogen-stimulated proliferation of MCF-7 cells at a lower concentration than TAM. In the absence of estradiol, TAT-59 and 4-OH-TAT-59 were effective at a lower concentration than that of 4-OH-Tamoxifen (4-OH-TAM), the active metabolite of TAM. In uterine growth inhibition, the effective dose of TAT-59 was about 3-6-fold lower than that of TAM, in various administration schedules. The minimum effective dose of TAT-59 against in vivo MCF-7 cells was about 3-fold lower than that of TAM. In DMBA-induced rat mammary tumors, TAT-59 inhibited the growth of existing tumors at about a 10-fold lower dose than TAM. Especially in the tumors with low ER levels (10-20 fmol/mg protein), TAT-59 showed a significantly stronger inhibitory effect than TAM. These experiments showed that TAT-59 was more effective in lower doses than TAM, even against the tumors with low ER content.

Original languageEnglish
Pages (from-to)397-404
Number of pages8
JournalEuropean Journal of Cancer and Clinical Oncology
Volume26
Issue number3
DOIs
Publication statusPublished - 1990 Mar
Externally publishedYes

ASJC Scopus subject areas

  • Oncology

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