Melatonin binding sites in estrogen receptor-positive cells derived from human endometrial cancer.
Our previous work showed that melatonin (N-acetyl-5-methoxytryptamine) inhibits proliferation of the human endometrial cancer cell line, Ishikawa, which is estrogen receptor-positive. The aim of the present study was to determine whether Ishikawa cells possess membrane melatonin receptors. Binding of the radioligand 2-[125I]-iodomelatonin to membrane preparations obtained from Ishikawa cells was detectable, saturable and stable. Scatchard analysis revealed that the dissociation constant (Kd) of the binding sites was 179.0 pm (similar to that of the MT2 [Mel1b] melatonin receptor subtype), and that the concentration (Bmax) of the binding sites was 12.9 fmol/mg protein. Luzindole, a selective MT2 melatonin receptor antagonist, significantly suppressed binding of 2-[125I]-iodomelatonin at all concentrations tested (10(-8) to 10(-4) m). These results suggest that the MT2 melatonin receptor subtype is present in the membranes of Ishikawa cells, and that the antiproliferative effect of melatonin on Ishikawa cells is mediated via the MT2 receptor. This may have implications for the use of melatonin in endometrial cancer therapy.
Kobayashi
Yoichi
Y
Department of Obstetrics and Gynecology, St Marianna University School of Medicine, Miyamae-ku, Kawasaki-city, Kanagawa, Japan. y5koba@marianna-u.ac.jp
Itoh
Masanori T
MT
Kondo
Haruhiro
H
Okuma
Yoshiaki
Y
Sato
Sojiro
S
Kanishi
Yosuke
Y
Hamada
Naomi
N
Kiguchi
Kazushige
K
Ishizuka
Bunpei
B
D001665:Binding Sites; D016889:Endometrial Neoplasms / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D006801:Humans; D008550:Melatonin / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D044094:Receptors, Melatonin / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D014363:Tryptamines / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D011960:Receptors, Estrogen; D044094:Receptors, Melatonin; D014363:Tryptamines; C057154:luzindole; D008550:Melatonin