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.
Lama
G
G
Istituto di Istologia ed Embriologia, Università Cattolica del Sacro Cuore, Rome, Italy.
Angelucci
C
C
Bruzzese
N
N
Iacopino
F
F
Nori
S L
SL
D'Atri
S
S
Turriziani
M
M
Bonmassar
E
E
Sica
G
G
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