Inhibition of murine osteosarcoma cell proliferation by glucocorticoid.
The effects of glucocorticoid (GC) on the proliferation of Dunn Osteosarcoma (OS) cells were examined under in vitro culture conditions. Dexamethasone (Dex) inhibited the proliferation of Dunn OS cells in a dose-dependent manner, while the addition of anti-GC, RU486, to the culture medium in part recovered Dex-induced growth inhibition. The number of maximum binding sites (Bmax) and the dissociation constant (Kd) value of glucocorticoid receptor (GR) in Dunn OS cells were 19,560 sites/cell and 5.2 +/- 0.8 nM, respectively. RU486 competed with labeled Dex against GR at a concentration of 10(-6) M. Western blot analysis of [3H]Dex-mesylate-labeled cell homogenate and immunohistochemical staining against GR further confirmed the presence of GR. Dex treatment of Dunn OS cells resulted in apoptosis with the characteristic internucleosomal DNA cleavage shown by the DNA ladder pattern in agarose gel electrophoresis. These data demonstrate that GC inhibits the proliferation of Dunn OS cells via GR, for which one possible mechanism in vitro is induction of apoptosis.
Yamamoto
Takashi
T
Department of Clinical Laboratory, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari, Osaka, 537-0025, Japan.
Nishiguchi
Miyuki
M
Inoue
Naokazu
N
Goto
Hiroe G
HG
Kudawara
Ikuo
I
Ueda
Takafumi
T
Yoshikawa
Hideki
H
Tanigaki
Yumiko
Y
Nishizawa
Yasuko
Y
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D006131:Growth Inhibitors; D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D014316:Tritium; D015735:Mifepristone; D003907:Dexamethasone