Antitumor effect of triphenylethylene derivative (TAT-59) against human breast carcinoma xenografts in nude mice.
The antitumor activity of a newly synthesized triphenylethylene derivative [(E)-4-[1-[4-[2-(dimethylamino)ethoxy-phenyl]-2-(4-isopropyl)phenyl-1- butenyl] phenyl monophosphate] (TAT-59) was investigated against human breast carcinoma xenografts in nude mice with reference to the changes of hormone receptors. Five strains (MCF-7, Br-10, R-27, ZR-75-1, and T-61) used for the experiments possessed cytosol estrogen receptor (ER), and their growth was estradiol dependent. Five mg of TAT-59 and tamoxifen citrate (TAM) per kg were administered p.o. daily except Sunday. TAT-59 showed a positive antitumor effect against MCF-7 and R-27, whereas TAM was effective on MCF-7, and their adverse effects detected by mortality rate, body weight loss, and spleen weight loss were similar to each other. The reduction of ER and production of progesterone receptor (PgR) after the treatment with TAT-59 were more potent than after TAM, suggesting that TAT-59 exerts its antitumor effect through binding to ER. These findings suggest that TAT-59 might merit use in clinical trials with breast cancers.
Koh
J
J
Department of Surgery, Social Insurance Saitama Chuo Hospital, Japan.
Kubota
T
T
Asanuma
F
F
Yamada
Y
Y
Kawamura
E
E
Hosoda
Y
Y
Hashimoto
M
M
Yamamoto
O
O
Sakai
S
S
Maeda
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D004965:Estrogen Antagonists / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011960:Receptors, Estrogen / Q000187:drug effects; D011980:Receptors, Progesterone / Q000187:drug effects; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; C064635:TAT 59