title: A new triphenylethylene derivative, TAT-59; hormone receptors; insulin-like growth factor 1; and growth suppression of hormone-dependent MCF-7 tumors in athymic mice.
abstract: TAT-59 ((E)-4-[1-[4-[2-(dimethylamino)ethoxy]-phenyl]-2-(4- isopropyl)phenyl-1-butenyl]-phenyl-monophosphate) treatment was performed on hormone-dependent MCF-7 tumors in athymic mice. TAT-59 given at 1, 5, and 20 mg/kg inhibited the estrogen-stimulated growth of MCF-7 tumors in athymic mice in a dose-dependent fashion. The most clear decrease in tumor growth was shown in the TAT-59 alone group, although it was not dramatic. Average serum concentrations of DP-TAT-59((Z)-[1-[4-[2-(dimethylamino)- ethoxy]phenyl]-2-(4-isopropyl)phenyl-1-butenyl]-4-hydroxybenzene) and DM-DP-TAT-59(desmethyl-DP-TAT-59), metabolites of TAT-59, increased in a dose-dependent manner. Much higher levels of DP-TAT-59 and DM-DP-TAT-59 were shown in tumors (target tissues of estrogen) as compared with muscles (nontarget tissues of estrogen) or serum. A serum concentration of DP-TAT-59 or DM-DP-TAT-59 corresponding to the physiologic levels of serum estradiol in premenopausal women was sufficient to inhibit the estrogen-stimulated growth of MCF-7 tumors in mice. TAT-59 induced a dose-dependent increase in estrogen receptor levels in the MCF-7 tumors. In contrast, it prevented the estradiol (E2)-induced increase in progesterone receptor levels in a dose-dependent manner. Insulin-like growth factor 1 levels measured in the MCF-7 tumors significantly decreased in the TAT-59 alone group and in the no treatment group as compared with the E2 alone group. These results show the pronounced antiestrogenic action of TAT-59 on hormone-dependent MCF-7 tumors in athymic mice.
authors.affiliation: Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Iino
authors.forename: Y
authors.initials: Y
authors.lastname: Takai
authors.forename: T
authors.initials: T
authors.lastname: Ando
authors.forename: S
authors.initials: S
authors.lastname: Ohwada
authors.forename: T
authors.initials: T
authors.lastname: Yokoe
authors.forename: N
authors.initials: N
authors.lastname: Sugamata
authors.forename: H
authors.initials: H
authors.lastname: Takei
authors.forename: J
authors.initials: J
authors.lastname: Horiguchi
authors.forename: K
authors.initials: K
authors.lastname: Iijima
authors.forename: Y
authors.initials: Y
authors.lastname: Morishita
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D004965:Estrogen Antagonists / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000187:drug effects*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009132:Muscles / Q000378:metabolism; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism; D011897:Random Allocation; D011960:Receptors, Estrogen / Q000187:drug effects*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use; D014599:Uterus / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen; C064635:TAT 59; C064590:2-(4-(1-(4-hydroxyphenyl)-2-(4-isopropylphenyl)-1-butenyl)phenoxy)-N,N-dimethylethylamine; D004958:Estradiol; D007334:Insulin-Like Growth Factor I