Sensitivity of human melanoma cells to oestrogens, tamoxifen and quercetin: is there any relationship with type I and II oestrogen binding site expression?
We investigated the effect of oestrogens, anti-oestrogens and flavonoids 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. 17beta-Oestradiol (E2) and the flavonoid quercetin (Q) produced a marked inhibition of proliferation, but only at the highest dose used (10(-5) M) and only when added daily to the medium. Diethylstilboestrol (DES) (10(-5) M) was effective in inhibiting cell growth when the medium was renewed every 3 days and produced a more pronounced reduction when added daily to the medium. Tamoxifen (TAM) inhibited cell proliferation at a dose starting from 10(-7) M when the medium was renewed 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) M and 10(-5) M. The antiproliferative effect of E2, DES and Q did not seem to be dependent on their interaction with ERs, which were minimally detected in SK-Mel-28 in both immunocytochemical and biochemical assays. Our model revealed, through a biochemical assay, a large number of type II EBSs which could be involved in the anti-oestrogen action, but this does not exclude the involvement of other mechanisms. Finally, TAM (10(-5) M) appeared to reduce the activity of the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase, an effect that could be interesting from the point of view of the therapeutic efficacy of alkylating agents.
Istituto di Istologia ed Embriologia, Università Cattolica del Sacro Cuore, Rome, Italy.
G
G
Lama
C
C
Angelucci
N
N
Bruzzese
F
F
Iacopino
S L
SL
Nori
S
S
D'Atri
M
M
Turriziani
E
E
Bonmassar
G
G
Sica
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004054:Diethylstilbestrol / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D008545:Melanoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D012878:Skin Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D004967:Estrogens; D005419:Flavonoids; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D013629:Tamoxifen; D004958:Estradiol; D004054:Diethylstilbestrol; D011794:Quercetin; D019853:O(6)-Methylguanine-DNA Methyltransferase