Dual effects of estrogen and antiestrogens on the growth of SK-N-MC human neuroblastoma cells.
The effects of estrogen (17-beta estradiol) and antiestrogens (tamoxifen, clomiphene and nafoxidine) on the growth of SK-N-MC human neuroblastoma cells were investigated. At low concentrations these agents enhanced, but at high concentrations they inhibited, the growth of the tumor cells in a dose-dependent manner. The growth inhibition was found to be due to decreased cell viability. When serum-free media were used, the dose-response curves were left-shifted, indicating that these agents can directly act on the tumor cells and that serum factors can inhibit their growth-modulatory actions. Growth enhancement and decreased cell viability induced by these agents were significantly reversed by the treatments with either Ca(2+)-free media, intracellular Ca2+ release blockers (dantrolene or ruthenium red) or BAPTA/AM, an intracellular Ca2+ chelator, implying that both intracellular Ca2+ release and extracellular Ca2+ entry may play a role in their growth regulation. These results suggest that estrogen and antiestrogens have concentration-dependent dual effects on the growth of the tumor cells and that the mechanism of their actions may be through the interaction with intracellular Ca2+ signalling mechanisms.
Department of Neurological Surgery, Loyola University Medical Center, Maywood, IL 60153.
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Lee
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Wurster
D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D016895:Culture Media, Serum-Free; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016895:Culture Media, Serum-Free; D004965:Estrogen Antagonists; D004958:Estradiol; D002118:Calcium