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

Abstract

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.