Ginsenoside Rg1 protects against 6-OHDA-induced neurotoxicity in neuroblastoma SK-N-SH cells via IGF-I receptor and estrogen receptor pathways.
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 microM 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 ER alpha 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.
Gao
Quan-Gui
QG
Department of Physiology, Medical College of Qingdao University, Qingdao, China.
Chen
Wen-Fang
WF
Xie
Jun-Xia
JX
Wong
Man-Sau
MS
D018663:Adrenergic Agents / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000633:toxicity*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D018663:Adrenergic Agents; D004791:Enzyme Inhibitors; D036145:Ginsenosides; D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D011960:Receptors, Estrogen; D051028:bcl-2-Associated X Protein; D016627:Oxidopamine; D017526:Receptor, IGF Type 1; C035054:ginsenoside Rg1