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.