Growth inhibition by danazol in a human endometrial cancer cell line with estrogen-independent progesterone receptors.
Since we recently found that danazol, an isoxazol derivative of ethinyltestosterone, has a growth-inhibitory effect on human endometrial cancer cells in primary culture, the effects of danazol on a human endometrial cancer cell line (IK-90 cells), which contains estrogen-independent progesterone receptors (PR), were investigated in the present study. The addition of danazol (1 nM-1 microM) in culture medium caused a decrease in the growth of IK-90 cells in a dose-dependent manner. Competitive binding studies showed that danazol effectively binds to PR in IK-90 cells, and the binding affinity for PR was estimated to be 6.0% of that of R5020. The addition of 1 microM danazol in culture medium resulted in a rapid and significant increase in nuclear PR with a concomitant decrease in cytoplasmic PR in the cells. These findings suggest that danazol has a growth-inhibitory effect on human endometrial adenocarcinoma cells directly through PR system in the cells.
Terakawa
N
N
Department of Obstetrics and Gynecology, Osaka University Medical School, Japan.
Ikegami
H
H
Shimizu
I
I
Aono
T
T
Tanizawa
O
O
Matsumoto
K
K
D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D003613:Danazol / Q000378:metabolism / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006801:Humans; D011245:Pregnadienes / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D014594:Uterine Neoplasms
D004967:Estrogens; D011245:Pregnadienes; D011944:Receptors, Androgen; D011980:Receptors, Progesterone; D013196:Dihydrotestosterone; D003613:Danazol