Inhibitory effect of the novel anti-estrogen EM-800 and medroxyprogesterone acetate on estrone-stimulated growth of dimethylbenz[a]anthracene-induced mammary carcinoma in rats.
The novel anti-estrogen EM-800 and medroxyprogesterone acetate (MPA) inhibit estrone (E1)-stimulated growth of dimethylbenz[a]anthracene (DMBA)-induced mammary tumors in a rat model. After 65 days, ovariectomy (OVX) decreased total tumor area to 9.6 +/- 3.9% of initial size, while E1 (1.0 microg, s.c., twice daily) stimulated tumor growth to 225 +/- 40.9% of initial size. Daily oral administration of 2.5 mg/kg body weight of EM-800 completely abolished E1-stimulated tumor growth. A low daily dose of EM-800 (0.25 mg/kg body weight) or MPA (1 mg, s.c., twice daily) used alone partially reversed the stimulatory effect of E1 on the growth of DMBA-induced tumors. The combination of both compounds, however, caused a more potent inhibitory effect than each compound used alone. A high dose of EM-800 completely or almost completely inhibited the E1-stimulated vaginal and uterine weights, respectively. The same dose of EM-800 completely reversed the inhibitory effect of E1 on serum luteinizing hormone levels. Uterine, vaginal and tumoral estrogen and progesterone receptor levels were reduced markedly following treatment with EM-800. Our data show that the combination of the pure anti-estrogen EM-800 with the androgenic compound MPA achieves greater inhibition of the growth of DMBA-induced mammary carcinoma than that achieved by each compound used alone.
Luo
S
S
Laboratory of Molecular Endocrinology, CHUL Research Center and Laval University, Québec, Canada.
Stojanovic
M
M
Labrie
C
C
Labrie
F
F
D015127:9,10-Dimethyl-1,2-benzanthracene; D000311:Adrenal Glands / Q000187:drug effects; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D002273:Carcinogens; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004970:Estrone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005260:Female; D007986:Luteinizing Hormone / Q000097:blood; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000139:chemically induced / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000187:drug effects; D011980:Receptors, Progesterone / Q000187:drug effects; D014599:Uterus / Q000737:chemistry / Q000187:drug effects; D014621:Vagina / Q000737:chemistry / Q000187:drug effects
D018931:Antineoplastic Agents, Hormonal; D001578:Benzopyrans; D002273:Carcinogens; D004965:Estrogen Antagonists; D011422:Propionates; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D004970:Estrone; D015127:9,10-Dimethyl-1,2-benzanthracene; D007986:Luteinizing Hormone; D017258:Medroxyprogesterone Acetate; C106945:EM 800