Inhibitory effect of a steroidal antiestrogen (EM-170) on estrone-stimulated growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in the rat.

Abstract

Recently, compounds having pure antiestrogenic activity have become available. In this study, we examined the activity of the new steroidal antiestrogen EM-170 (N-n-butyl, N-methyl-11-(16' alpha-chloro-3',17' alpha-dihydroxy-estra-1',3',5'-(10')-trien-7' alpha-yl) undecanamide) on the growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma stimulated by treatment with estrone (E1), a steroid known to play an important role as precursor of 17 beta-estradiol (E2), especially in postmenopausal women. Twenty-five days after ovariectomy (OVX), tumor volume in control OVX animals decreased to 51.4 +/- 11% of the initial volume; treatment with E1, administered by Silastic implants, stimulated tumor growth to 179 +/- 21%. Treatment with the antiestrogen EM-170 at a dose of 200 micrograms (twice daily) not only completely reversed the stimulatory effect of E1, but also inhibited tumor growth to 30.5 +/- 9.6%, an effect that is 41% (P < 0.01 vs OVX control) greater than that of ovariectomy alone. At a relatively low dose of 40 micrograms (twice daily), 20 days of treatment with EM-170 reversed by 55% the stimulatory effect of E1 (1.0 micrograms, subcutaneously, twice daily) on tumor growth in OVX animals. On the other hand, the antiestrogen also induced a significant inhibitory effect on 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity in the DMBA-induced mammary tumors, an effect that is in agreement with the marked reduction caused by the same treatment on tumor estradiol (E2) levels in E1-treated OVX animals.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: F Labrie, S Li, C Labrie, C Lévesque, Y Mérand
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 33 Issue 3 Pg. 237-44 (Mar 1995) ISSN: 0167-6806 [Print] Netherlands
• PMID: 7749151 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Estrogen Antagonists
• EM 139
• Estrone
• Estradiol
• 9,10-Dimethyl-1,2-benzanthracene
• 17-Hydroxysteroid Dehydrogenases

Topics

• 17-Hydroxysteroid Dehydrogenases (analysis)
• 9,10-Dimethyl-1,2-benzanthracene
• Animals
• Estradiol (analogs & derivatives, pharmacology)
• Estrogen Antagonists (pharmacology)
• Estrone (antagonists & inhibitors)
• Female
• Mammary Neoplasms, Experimental (chemically induced, drug therapy, enzymology)
• Rats
• Rats, Sprague-Dawley