Comparative pharmacodynamic analysis of TAT-59 and tamoxifen in rats bearing DMBA-induced mammary carcinoma

Toshiyuki Toko, Jiro Shibata, Yoshikazu Sugimoto, Hidetoshi Yamaya, Masahiko Yoshida, Kazuo Ogawa, Eiji Matsushima

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

TAT-59 suppressed the growth fo DMBA-induced mammary tumors in rats earlier and more strongly than tamoxifen (TAM). After oral administration of the drugs, DP-TAT-59, one of the main metabolites of TAT-59, was found in 10- to 15-fold higher concentrations in both the tumor and blood compared to 4-OH-TAM, an active metabolite of TAM. In a 3-day antiuterotrophic test, every detected metabolite of TAT-59 showed stronger antiestrogenic activity than did TAM. In a competition assay, the affinity of the metabolites for estrogen receptors ranged from that of estradiol to that of TAM. These results suggest that the superior antiestrogenic activity of TAT-59 compared to TAM was either due to its higher penetration into tumor tissue or to the stronger antiestrogenic activity of its metabolites.

Original languageEnglish
Pages (from-to)7-13
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume37
Issue number1-2
DOIs
Publication statusPublished - 1995 Jan
Externally publishedYes

Fingerprint

Bearings (structural)
Pharmacodynamics
9,10-Dimethyl-1,2-benzanthracene
Tamoxifen
Rats
Metabolites
Breast Neoplasms
Tumors
Estrogen Receptors
Oral Administration
TAT 59
Estradiol
Assays
Neoplasms
Blood
Tissue
Growth

Keywords

  • Anti-estrogenic activity
  • DMBA-induced mammary tumor
  • Pharmacodynamics
  • TAT-59

ASJC Scopus subject areas

  • Pharmacology
  • Oncology
  • Cancer Research

Cite this

Comparative pharmacodynamic analysis of TAT-59 and tamoxifen in rats bearing DMBA-induced mammary carcinoma. / Toko, Toshiyuki; Shibata, Jiro; Sugimoto, Yoshikazu; Yamaya, Hidetoshi; Yoshida, Masahiko; Ogawa, Kazuo; Matsushima, Eiji.

In: Cancer Chemotherapy and Pharmacology, Vol. 37, No. 1-2, 01.1995, p. 7-13.

Research output: Contribution to journalArticle

Toko, Toshiyuki ; Shibata, Jiro ; Sugimoto, Yoshikazu ; Yamaya, Hidetoshi ; Yoshida, Masahiko ; Ogawa, Kazuo ; Matsushima, Eiji. / Comparative pharmacodynamic analysis of TAT-59 and tamoxifen in rats bearing DMBA-induced mammary carcinoma. In: Cancer Chemotherapy and Pharmacology. 1995 ; Vol. 37, No. 1-2. pp. 7-13.
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