Involvement of glucocorticoid receptor in the induction of differentiation by ginsenosides in F9 teratocarcinoma cells.
We have previously reported that ginsenosides Rh1 and Rh2 induced the differentiation of F9 teratocarcinoma stem cells [Lee, Y. N., Lee, H. Y., Chung, H. Y., Kim, S. I., Lee, S. K., Park, B. C. and Kim, K. W., In vitro induction of differentiation by ginsenosides in F9 teratocarcinoma cells. Eur. J. Cancer 1996, 32, 1420-1428.]. Since the chemical structure of Rh1 and Rh2 is very similar to that of dexamethasone, a synthetic glucocorticoid, we investigated whether Rh1 and Rh2 act through the glucocorticoid receptor (GR). Immunocytochemistry showed that Rh1 or Rh2 increased the nuclear translocation of GR in the same manner of dexamethasone. In the gel shift assay, glucocorticoid response element (GRE) binding protein in F9 cells was increased by Rh1 or Rh2. To confirm whether the increased binding protein is GR, we performed the competition assay with unlabeled GRE as a specific competitor. Moreover, supershift assay with the GR antibody showed that the binding proteins are GR. In addition, to confirm the Rh1 or Rh2-induced transactivation of GRE promoter, we cotransfected GR expression vector and GRE-luciferase vector. In the luciferase assay, Rh1 or Rh2 potently induced luciferase activity and this induction was blocked by RU486, a potent GR antagonist. Taken together, we suggest that ginsenosides Rh1 and Rh2 may induce the differentiation of F9 cells by stimulating the nuclear translocation of GR.
Lee
Y N
YN
Department of Molecular Biology, Pusan National University, South Korea.
Lee
H Y
HY
Lee
Y M
YM
Chung
H Y
HY
Kim
S I
SI
Lee
S K
SK
Park
B C
BC
Kim
K W
KW
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002491:Central Nervous System Agents / Q000494:pharmacology*; D036145:Ginsenosides; D051379:Mice; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D018243:Teratocarcinoma / Q000378:metabolism* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D002491:Central Nervous System Agents; D036145:Ginsenosides; D011965:Receptors, Glucocorticoid; D012503:Saponins