SENSITIVITY OF HUMAN-MELANOMA CELLS TO ESTROGENS, TAMOXIFEN AND QUERCETIN - IS THERE ANY RELATIONSHIP WITH TYPE-I AND TYPE-II ESTROGEN-BINDING SITE EXPRESSION

We investigated the effect of oestrogens, anti-oestrogens and flavonoi ds on the growth of a human melanoma cell line (SK-Mel-28) and, at the same time, the presence of both type I oestrogen receptors (ERs) and type II oestrogen binding sites (type II EBS) to gain a fuller picture of the relationship between melanoma cell proliferation and receptor status. 17 beta-Oestradiol (E-2) end the flavonoid quercetin (Q) produ ced a marked inhibition of proliferation, but only at the highest dose used (10(-5) M) and only when added daily to the medium. Diethylstilb oestrol (DES) (10(-5) M) was effective in inhibiting cell growth when the medium was renewed every 3 days and produced a more pronounced red uction when added daily to the medium. Tamoxifen (TAM) inhibited cell proliferation at a dose starting from 10(-7) M when the medium was ren ewed every 3 days. When added daily to the medium, it did not induce a greater inhibitory effect and it was cytotoxic at 5 x 10(-6) nn and 1 0(-5) M. The antiproliferative effect of E-2, DES and Q did not seem t o be dependent on their interaction with ERs, which were minimally det ected in SK-Mel-28 in both immunocytochemical and biochemical assays. Our model revealed, through a biochemical assay, a large number of typ e II EBSs which could be involved in the anti-oestrogen action, but th is does not exclude the involvement of other mechanisms. Finally, TAM (10(-5) M) appeared to reduce the activity of the DNA repair enzyme O- 6-alkylguanine-DNA alkyltransferase, an effect that could be interesti ng from the point of view of the therapeutic efficacy of alkylating ag ents. (C) 1998 Lippincott Williams & Wilkins.