Premium
Ginsenoside Rg1 protects against 6‐OHDA‐induced neurotoxicity in neuroblastoma SK‐N‐SH cells via IGF‐I receptor and estrogen receptor pathways
Author(s) -
Gao QuanGui,
Chen WenFang,
Xie JunXia,
Wong ManSau
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06051.x
Subject(s) - neurotoxicity , estrogen receptor , neuroprotection , pharmacology , chemistry , receptor , apoptosis , antagonist , medicine , biology , biochemistry , toxicity , cancer , breast cancer
Our previous studies have demonstrated that ginsenoside Rg1 is a novel class of potent phytoestrogen and can mimic the action of estradiol in stimulation of MCF‐7 cell growth by the crosstalk between insulin‐like growth factor‐I receptor (IGF‐IR)‐dependent pathway and estrogen receptor (ER)‐dependent pathway. The present study was designed to investigate the neuroprotective effects of ginsenoside Rg1 against 6‐hydroxydopamine (6‐OHDA)‐induced neurotoxicity in human neuroblastoma SK‐N‐SH cells and the possible mechanisms. Pre‐treatment with ginsenoside Rg1 resulted in an enhancement of survival, and significant rescue occurred at the concentration of 0.01 μM on cell viability against 6‐OHDA‐induced neurotoxicity. These effects could be completely blocked by IGF‐IR antagonist JB‐1 or ER antagonist ICI 182780. 6‐OHDA arrested the cells at G 0 G 1 phase and prevented S phase entry. Rg1 pre‐treatment could reverse the cytostatic effect of 6‐OHDA. Ginsenoside Rg1 also could attenuate 6‐OHDA‐induced decrease in mitochondrial membrane potential. These effects could also be completely blocked by JB‐1 or ICI 182780. Furthermore, 6‐OHDA‐induced up‐regulation of Bax and down‐regulation of Bcl‐2 mRNA and protein expression could be restored by Rg1 pre‐treatment. Rg1 pre‐treatment could reverse the down‐regulation of ERα protein expression induced by 6‐OHDA treatment. Cells transfected with the estrogen responsive element (ERE)‐luciferase reporter construct exhibited significantly increased ERE‐luciferase activity in the Rg1 presence, suggesting that the estrogenic effects of Rg1 were mediated through the endogenous ERs. These results suggest that ginsenoside Rg1 may attenuate 6‐OHDA‐induced apoptosis and its action might involve the activation of IGF‐IR signaling pathway and ER signaling pathway.