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

Int J Cancer. 1997 Nov 14;73(4):580-6. doi: 10.1002/(sici)1097-0215(19971114)73:4<580::aid-ijc20>3.0.co;2-c.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Adrenal Glands / drug effects
  • Animals
  • Antineoplastic Agents, Hormonal / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Benzopyrans / pharmacology*
  • Carcinogens
  • Cell Division / drug effects
  • Drug Screening Assays, Antitumor
  • Estrogen Antagonists / pharmacology*
  • Estrone / antagonists & inhibitors*
  • Estrone / pharmacology
  • Female
  • Luteinizing Hormone / blood
  • Mammary Neoplasms, Experimental / blood
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / chemistry
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / pathology
  • Medroxyprogesterone Acetate / pharmacology*
  • Organ Size / drug effects
  • Propionates / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Estrogen / drug effects
  • Receptors, Progesterone / drug effects
  • Uterus / chemistry
  • Uterus / drug effects
  • Vagina / chemistry
  • Vagina / drug effects

Substances

  • Antineoplastic Agents, Hormonal
  • Benzopyrans
  • Carcinogens
  • Estrogen Antagonists
  • Propionates
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Estrone
  • 9,10-Dimethyl-1,2-benzanthracene
  • Luteinizing Hormone
  • Medroxyprogesterone Acetate
  • EM 800