HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Effects of antiandrogens on growth of androgen-dependent mouse mammary tumor (Shionogi carcinoma 115) in vivo and in vitro.

Abstract
Binding affinities of modified steroidal anthrasteroids, 3 beta-hydroxy-3a beta,6-dimethyl-2,3,3a,4,5,8,9,10,10a beta,11,11a beta, 11b alpha-dodecahydro-1H-cyclopenta[a]anthracene-8-one (1) and 3a beta,6-dimethyl-2,3,3a,4,5,8,9,10,10a beta,11,11a beta,11b alpha-dodecahydro-1H-cyclopenta[a]anthracene-3,8-dione (2), the steroid oxendolone and the nonsteroid AA560, for the androgen receptor (AR) of Shionogi carcinoma 115 (SC115) and their effects on the growth of SC115 were investigated in vivo and in vitro. The inhibitory effects of these compounds on testosterone 5 alpha-reductase of SC115 tissues were also measured. The relative binding affinities of these compounds were 3.17-0.03% of that of dihydrotestosterone, and their rank order was (1) greater than AA560 greater than oxendolone much greater than (2). In the presence of 10(-9) M testosterone, anthrasteroids and AA560 inhibited the growth of SC115 cells at 10(-7) M in a serum-free medium, but oxendolone did not. In the absence of testosterone, (1), (2) and oxendolone promoted cell growth at 10(-6), 10(-7) and 10(-7) M, respectively. However, AA560 nearly completely blocked cell growth at 10(-5) M. At a 2 mg daily dose for 13 days, (1) and AA560 powerfully inhibited tumor growth in castrated DS mice treated with testosterone propionate but oxendolone had almost no effect. Anthrasteroids and oxendolone showed weak but significant agonistic activity in vivo. Anthrasteroids markedly inhibited 5 alpha-reductase activity of SC115, oxendolone weakly and AA560 not at all. The remarkable antiandrogenic activities of (1) and AA560 may partially result from their higher affinities for the AR of SC115 but other yet unknown mechanisms may also contribute to these activities.
AuthorsT Suzuki, I Horibe, N Uchida, K Ezumi, K Uchida, K Takeda, A Tanaka, Y Nishizawa, K Matsumoto
JournalThe Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 37 Issue 4 Pg. 559-67 (Nov 30 1990) ISSN: 0960-0760 [Print] England
PMID2278840 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • 5-alpha Reductase Inhibitors
  • Androgen Antagonists
  • Aniline Compounds
  • Receptors, Androgen
  • Steroids
  • 3-hydroxy-3,6-dimethyl-2,3,3,4,5,8,9,10,10,11,11,11-dodecahydro-1H-cyclopenta(a)anthracene-8-one
  • 3,6-dimethyl-2,3,3a,4,5,8,9,10,10,11,11,11-dodecahydro-1H-cyclopenta(a)anthracene-3,8-dione
  • AA 560
  • Nandrolone
  • oxendolone
Topics
  • 5-alpha Reductase Inhibitors
  • Androgen Antagonists (therapeutic use)
  • Aniline Compounds (metabolism, pharmacology, therapeutic use)
  • Animals
  • Cell Division (drug effects)
  • Male
  • Mammary Neoplasms, Experimental (drug therapy, metabolism, pathology)
  • Mice
  • Nandrolone (analogs & derivatives, metabolism, pharmacology, therapeutic use)
  • Receptors, Androgen (metabolism)
  • Steroids (metabolism, pharmacology, therapeutic use)
  • Tumor Cells, Cultured

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: