Ginsenoside Rh2 Mitigates Pediatric Leukemia Through Suppression of Bcl-2 in Leukemia Cells.
OBJECTIVE
Acute myeloid leukemia (AML) is a severe malignant cancer worldwide, in both adult and pediatric patients. Since bone marrow cell transplantation is seriously limited by the availability of the immune-paired donor sources, the therapy for pediatric leukemia remains challenging. Ginsenoside Rh2 (GRh2) is a well-characterized component in red ginseng, and has established therapeutic effects for different diseases, although whether GRh2 may have a therapeutic effect on pediatric leukemia has not been investigated.


METHODS
We examined the effects of GRh2 on the survival of mice in an acute leukemia model. We analyzed the effects of GRh2 on the cell viability of leukemia cell lines in vitro, using a CCK-8 assay and an MTT assay. We analyzed the effects of GRh2 on the apoptosis of leukemia cell lines in vitro, by flow cytometry. We analyzed the levels of Bcl-2 and microRNA-21 (miR-21) in GRh2-treated leukemia cells. Prediction of binding between miR-21 and 3'-UTR of Bcl-2 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay.


RESULTS
GRh2 significantly prolonged the survival of mice with pediatric leukemia. GRh2 significantly decreased the viability of leukemia cells in vitro, through induction of apoptosis. GRh2 significantly decreased the levels of an anti-apoptotic protein Bcl-2 in leukemia cells, possibly through induction of miR-21, which suppressed the translation of Bcl-2 mRNA via 3'-UTR binding.


CONCLUSIONS
GRh2 may be an effective treatment for pediatric leukemia, and GRh2 may induce apoptosis of leukemia cells through miR-21-modulated suppression of Bcl-2.
Xiaoru
X
Wang
Yulin
Y
Wang
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D036145:Ginsenosides / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D009368:Neoplasm Transplantation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis
D000972:Antineoplastic Agents, Phytogenic; D036145:Ginsenosides; C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; C055305:ginsenoside Rh2