Contrasting effects of alpha- and beta-androstenediol on oncogenic myeloid cell lines in vitro.
The in vitro effects of 17 alpha AED, the isomer of 5-androstene-3 beta,17 beta diol (17 beta AED) on the basal growth of murine RAW 264.7, P388D1, and human HL-60 cells were investigated. 17 alpha AED treatment of RAW cells for 48 h reduced total cell number without increasing cell death as detected by trypan blue exclusion. At these doses, DNA synthesis as measured by [3H]thymidine incorporation was suppressed by as much as 65%, P < 0.05. This effect was time- and dose-dependent and reversible on removal of the steroid. Similar results were obtained with P388D1 and human HL-60 cell lines. At 50 nM or above, 17 alpha AED induced apoptosis in RAW cells and HL-60 as detected by transmission electron microscopy and TUNEL assays. By contrast, treating cells with the isomer 17 beta AED had no such effect. These data suggest that the balance between the anti-proliferative effect of 17 alpha AED and the proliferative effects of 17 beta AED may determine the overall level of myelopoiesis.
Huynh
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Department of Microbiology and Immunology, Virginia Commonwealth University, Medical College of Virginia, Richmond 23298-09678, USA.
Loria
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D015114:Androstenediol / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology; D053938:DNA Fragmentation; D006131:Growth Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D008264:Macrophages / Q000166:cytology; D051379:Mice; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D006131:Growth Inhibitors; D015114:Androstenediol; D000242:Cyclic AMP