Ginsenoside Rg1 induces apoptosis through inhibition of the EpoR-mediated JAK2/STAT5 signalling pathway in the TF-1/ Epo human leukemia cell line.
Ginsenoside Rg1 is one effective anticancer and antioxidant constituent of total saponins of Panax ginseng (TSPG), which has been shown to have various pharmacological effects. Our previous study demonstrated that Rg1 had anti-tumor activity in K562 leukemia cells. The aim of this study was designed to investigate whether Rg1 could induce apoptosis in TF-1/Epo cells and further to explore the underlying molecular mechanisms. Here we found that Rg1 could inhibit TF-1/Epo cell proliferation and induce cell apoptosis in vitro in a concentration and time dependent manner. It also suppressed the expression of EpoR on the surface membrane and inhibited JAK2/STAT5 pathway activity. Rg1 induced up-regulation of Bax, cleaved caspase-3 and C-PAPR protein and down-regulation of Bcl-2 and AG490, a JAK2 specific inhibitor, could enhance the effects of Rg1. Our studies showed that EpoR-mediated JAK2/STAT5 signaling played a key role in Rg1-induced apoptosis in TF-1/Epo cells. These results may provide new insights of Rg1 protective roles in the prevention a nd treatment of leukemia.
Laboratory of Stem Cells and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing, China E-mail : chendilong@21cn.com.
Jing
J
Li
Qiang
Q
Wei
Guo-Wei
GW
Zuo
Jing
J
Xia
Zhi-Mei
ZM
You
Chun-Li
CL
Li
Di-Long
DL
Chen
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002491:Central Nervous System Agents / Q000494:pharmacology; D004921:Erythropoietin / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017467:Receptors, Erythropoietin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D002491:Central Nervous System Agents; D036145:Ginsenosides; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D050799:STAT5 Transcription Factor; D004921:Erythropoietin; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C035054:ginsenoside Rg1