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2126348 
Journal Article 
ANTITUMOR EFFECTS OF DROLOXIFENE, A NEW ANTIESTROGEN DRUG, AGAINST 7,12-DIMETHYLBENZ(A)ANTHRACENE-INDUCED MAMMARY-TUMORS IN RATS 
Kawamura, I; Mizota, T; Kondo, N; Shimomura, K; Kohsaka, M 
1991 
Yes 
Japanese Journal of Pharmacology
ISSN: 0021-5198
EISSN: 1347-3506 
57 
2 
215-224 
English 
1812300 
WOS:A1991GM55100010 
The antitumor effects of droloxifene (DROL, (E)-alpha-[p-[2-(dimethyl amino)ethoxy]-phenyl]-alpha'-ethyl-3-stilbenol), a new antiestrogen drug, on 7,12-dimethylbenz(a)antracene (DMBA)-induced estrogen-dependent mammary tumors in rats were studied and compared with those of tamoxifen (TAM). Mammary tumors appeared from about 2 months after p.o. administration of DMBA to female rats, and all of them were estrogen receptor (ER) and progesterone receptor positive. DROL and TAM (p.o.) inhibited the growth of the tumors. Both drugs inhibited the binding of I-125-estradiol-17-beta to ER in the cytosol of the tumor in vitro, and the effect of DROL was much stronger than that of TAM. When H-3-estradiol-17-beta (H-3-E2) was given s.c. to rats with the mammary tumors, H-3-E2 accumulated in the tumors, uteri and vaginae in which the ER levels are known to be high, but was low in the heart, in which the ER levels are normally low. DROL and TAM decreased the levels of H-3-E2 in the tumors, uteri and vaginae, but had no effect in the hearts. When DROL or TAM was given p.o. to rats daily for 7 consecutive days after administration of DMBA, they inhibited the induction of mammary tumors by DMBA. From these results, DROL inhibits the growth and the initiation of DMBA-induced mammary tumors by inhibiting the binding of estrogen to its receptor.