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 (tamoxif en, clomiphene and nafoxidine) on the growth of SK-N-MC human neurobla stoma cells were investigated. At low concentrations these agents enha nced, but at high concentrations they inhibited, the growth of the tum or cells in a dose-dependent manner. The growth inhibition was found t o be due to decreased cell viability. When serum-free media were used, the dose-response curves were left-shifted, indicating that these age nts can directly act on the tumor cells and that serum factors can inh ibit their growth-modulatory actions. Growth enhancement and decreased cell viability induced by these agents were significantly reversed by the treatments with either Ca2+-free media, intracellular Ca2+ releas e blockers (dantrolene or ruthenium red) or BAPTA/AM, an intracellular Ca2+ chelator, implying that both intracellular Ca2+ release and extr acellular Ca2+ entry may play a role in their growth regulation. These results suggest that estrogen and antiestrogens have concentration-de pendent dual effects on the growth of the tumor cells and that the mec hanism of their actions may be through the interaction with intracellu lar Ca2+ signalling mechanisms.