17 alpha androstenediol inhibition of breast tumor cell proliferation in estrogen receptor-positive and -negative cell lines.
Androstene-3beta, 17alpha-diol (17alpha-AED) inhibits DNA synthesis and induces apoptosis in several myeloid cancer cell lines. The purpose of this study was to determine if 17alpha-AED inhibition of human breast carcinoma cell proliferation is dependent on the estrogen or androgen receptor. At concentrations of 12.5 to 50 x 10(-9) M 17alpha-AED inhibited the proliferation of ZR75-1, estrogen receptor-positive (ER+) cells, by 54% to 68%. Further, 17alpha-AED inhibited MDA-MB231, estrogen receptor-negative (ER-) cells, by 33.6% to 56.0%. The inhibitory effect was dose dependent with a minimal effective inhibitory dose at 12.5x10(-9) M for both cell lines. Both 17beta-AED and estradiol potentiate the inhibitory effect of 17alpha-AED on ER+ cells at lower doses (3.13 to 6.25 x 10(-9) M) where 17alpha-AED alone was not inhibitory. The inhibitory action of 17alpha-AED on human mammary carcinomas appears to be independent of either the alpha estrogen or the androgen receptors.
Huynh
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Department of Microbiology, Virginia Commonwealth University, Medical College of Virginia, Richmond 23298, USA.
Carter
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Loria
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D045930:Anabolic Agents / Q000494:pharmacology*; D000726:Androgen Antagonists / Q000494:pharmacology; D059002:Androgen Receptor Antagonists; D015114:Androstenediol / Q000494:pharmacology*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D005485:Flutamide / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D011944:Receptors, Androgen / Q000502:physiology; D011960:Receptors, Estrogen / Q000502:physiology*; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D045930:Anabolic Agents; D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D018931:Antineoplastic Agents, Hormonal; D047628:Estrogen Receptor alpha; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D004958:Estradiol; D005485:Flutamide; D015114:Androstenediol