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10 February 2020 : Laboratory Research  

Ginsenoside Rg1 Inhibits Cell Proliferation and Induces Markers of Cell Senescence in CD34+CD38– Leukemia Stem Cells Derived from KG1α Acute Myeloid Leukemia Cells by Activating the Sirtuin 1 (SIRT1)/Tuberous Sclerosis Complex 2 (TSC2) Signaling Pathway

Yan-Long Tang1BCDEF, Cheng-Gui Zhang2BCDEF, Heng Liu2BCDF, Yue Zhou3ABDEG*, Ya-Ping Wang4BCDF, Yuan Li3BCF, Yan-Jun Han3BF, Cui-Li Wang3BC

DOI: 10.12659/MSM.918207

Med Sci Monit 2020; 26:e918207

Abstract

BACKGROUND: Clinical relapse in acute myeloid leukemia (AML) is associated with the reduced treatment response of leukemia stem cells (LSCs). This study aimed to investigate the effects of the ginseng derivative, ginsenoside Rg1 (Rg1), on CD34+CD38– LSCs derived from KG1a human acute myeloid leukemia cells.

MATERIAL AND METHODS: CD34+CD38– LSCs were isolated from KG1a human acute myeloid leukemia cells by cell sorting. CD34+CD38– KG1α LSCs were divided into the control group and the Rg1 group (treated with Rg1). The cell counting kit-8 (CCK-8) assay evaluated the proliferation of CD34+CD38– KG1α LSCs and flow cytometry studied the cell cycle. The mixed colony-forming unit (CFU-Mix) assay and staining for senescence-associated beta-galactosidase (SA-β-Gal) evaluated cell senescence. Expression of sirtuin 1 (SIRT1) and tuberous sclerosis complex 2 (TSC2) were evaluated using Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR).

RESULTS: CD34+CD38– KG1α LSCs were isolated at 98.72%. Rg1 significantly reduced the proliferation of CD34+CD38– KG1α LSCs compared with the control group (p<0.05). Cells in the G0/G1 phase were significantly increased, and cells in the G2/M and S phase were significantly reduced compared with the control group (p<0.05). Rg1 significantly increased SA-β-Gal and reduced CFU-Mix formation compared with the control group (p<0.05), significantly down-regulated SIRT1 expression in CD34+CD38– KG1α LSCs compared with the control group (p<0.05), and significantly reduced TSC2 expression in CD34+CD38– KG1α LSCs compared with the control group (p<0.05).

CONCLUSIONS: Rg1 inhibited cell proliferation and induced cell senescence markers in CD34+CD38– KG1α LSCs by activating the SIRT1/TSC2 signaling pathway.

Keywords: adult stem cells, Ginsenosides, Leukemia, Myeloid, Acute, ADP-ribosyl Cyclase 1, Antigens, CD34, Biomarkers, Tumor, Cell Cycle, Cellular Senescence, Down-Regulation, Neoplastic Stem Cells, Sirtuin 1, Tuberous Sclerosis, beta-Glucosidase

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750