TAMOXIFEN AND QUERCETIN INTERACT WITH TYPE-II ESTROGEN-BINDING SITES AND INHIBIT THE GROWTH OF HUMAN-MELANOMA CELLS

The mechanism of the antiproliferative activity of tamoxifen on melano ma cells in vitro and in vivo is poorly understood, as it is not media ted by the antiestrogenic properties of tamoxifen. Using a whole-cell assay and nuclear and cytosolic radiobinding experiments with [H-3]-es tradiol as tracer, we found that MNT1, M10, and M14 melanoma cell line s as well as primary tumors expressed type II estrogen binding sites t hat bind tamoxifen and the flavonoid quercetin with similar affinity ( K-D 10-25 nM). Cell count and clonogenic assay showed both compounds t o inhibit melanoma cell growth in a concentration-dependent manner in the range of concentrations between 1 nM and 1 mu M. Neither the pure antiestrogen ICI-182780 nor the 3-rhamnosylglucoside of quercetin, rut in, bound to type II estrogen binding sites or inhibited cell growth. Our results suggesting that tamoxifen and quercetin can inhibit melano ma cell growth by interacting with type II estrogen binding sites help explain the reported effectiveness of tamoxifen, particularly in estr ogen-receptor-negative tumors, and stress the potential role of querce tin in the treatment of melanoma.