Glucocorticoid receptor-induced down-regulation of MMP-9 by ginseng components, PD and PT contributes to inhibition of the invasive capacity of HT1080 human fibrosarcoma cells.
We examined the effects of the purified ginseng components, panaxadiol (PD) and panaxatriol (PT), on the expression of matrix metalloproteinase-9 (MMP-9) in highly metastatic HT1080 human fibrosarcoma cell line. A significant down-regulation of MMP-9 by PD and PT was detected by Northern blot analysis. However, the expression of MMP-2 was not changed by treatment with PD and PT. Quantitative gelatin based zymography confirmed a markedly reduced expression of MMP-9, but not MMP-2 in the treatment of PD and PT. To investigate whether the reduced level of MMP-9 by PD and PT affects the invasive capacity of HT1080 cells, we conducted an in vitro invasion assay with PD and PT treated cells. The results of the in vitro invasion assay revealed that PD and PT reduced tumor cell invasion through a reconstituted basement membrane in the transwell chamber. Because of the similarity of chemical structure between PD, PT and dexamethasone (Dexa), a synthetic glucocorticoid, we investigated whether the down-regulation of MMP-9 by PD and PT were mediated by the nuclear translocation of glucocorticoid receptor (GR). Increased GR in the nucleus of HT1080 human fibrosarcoma cells treated by PD and PT was detected by immunocytochemistry. Western blot and gel retardation assays confirmed the increase of GR in the nucleus after treatment with PD and PT. These results suggest that GR-induced down-regulation of MMP-9 by PD and PT contributes to reduce the invasive capacity of HT1080 cells.
Park
M T
MT
Department of Molecular Biology and Pusan Cancer Research Center, Pusan National University, Korea.
Cha
H J
HJ
Jeong
J W
JW
Kim
S I
SI
Chung
H Y
HY
Kim
N D
ND
Kim
O H
OH
Kim
K W
KW
D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D003907:Dexamethasone / Q000737:chemistry; D004790:Enzyme Induction / Q000187:drug effects; D005354:Fibrosarcoma / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D036145:Ginsenosides; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D005894:Panax / Q000737:chemistry*; D010946:Plants, Medicinal; D012333:RNA, Messenger / Q000096:biosynthesis; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D036145:Ginsenosides; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D014315:Triterpenes; C028697:dexamethasone receptor; C004564:panaxadiol; D003907:Dexamethasone; C004563:panaxatriol; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9