Inhibition of growth and appearance of estrogen-dependent rat mammary tumors by 10-propargylestr-4-ene-3,17-dione, an aromatase inhibitor.

Abstract

The aromatase inhibitor 10-propargylestr-4-ene-3,17-dione (PED) has been evaluated in vivo as an anticancer agent. Prolonged administration of PED to rats bearing dimethylbenzanthracene-induced mammary tumors resulted in significant regression of hormone-responsive tumors within several days. Greater than 50% regression was generally observed after 14 days of treatment, irrespective of dose (1, 5, or 50 mg/kg body weight/day). In addition to tumor regression, a significantly increased incidence in tumor stasis was observed over the course of PED treatment. While all doses of PED examined were equipotent for both tumor regression and stasis, a dose-dependent inhibition of new tumor formation was observed in PED-treated rats. In control animals an average of 1.2 new tumors was observed during the experimental period; in contrast, averages of 0.5 tumors appeared in animals receiving 1 mg PED/kg body weight/day, 0.1 tumors at 5 mg/kg, and at 50 mg of PED/kg body weight/day, no new tumors occurred during the time PED was administered. The effects of PED on both regression of existing tumors and appearance of new tumors were reversed by co-administration of estradiol. Thus, PED impairs estrogen-dependent mammary tumor growth, resulting in cessation of new growth and regression of responsive tumors.

• Authors: S J Zimniski, M E Brandt, D F Covey, D Puett
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 26 Issue 1 Pg. 15-21 ( 1993) ISSN: 0167-6806 [Print] Netherlands
• PMID: 8400320 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Aromatase Inhibitors
• Estrogens
• Androstenedione
• Estradiol
• 9,10-Dimethyl-1,2-benzanthracene
• Pargyline
• plomestane

Topics

• 9,10-Dimethyl-1,2-benzanthracene
• Androstenedione (analogs & derivatives, pharmacology)
• Animals
• Antineoplastic Agents (pharmacology)
• Aromatase Inhibitors
• Cell Division (drug effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Estradiol (pharmacology)
• Estrogens
• Estrus (drug effects)
• Female
• Mammary Neoplasms, Experimental (chemically induced, drug therapy, enzymology)
• Neoplasms, Hormone-Dependent (chemically induced, drug therapy, enzymology)
• Pargyline (analogs & derivatives, pharmacology)
• Rats
• Rats, Sprague-Dawley