Ginsenoside Rg1 induces senescence of leukemic stem cells by upregulating p16INK4a and downregulating hTERT expression

Abstract

Background. Leukemic stem cells (LSCs) play an important role in the pathogenesis of leukemia. This research attempted to clarify effects of the telomere system on ginsenoside Rg1-induced senescence of LSCs. Objectives. This research attempted to clarify effects of the telomere system on ginsenoside Rg1-induced senescence of LSCs. Materials and methods. CD34+CD38− LSCs were isolated, sorted, and divided into a control group and a Rg1 group (treated with 40 μmol/L Rg1). Cell Counting Kit-8 (CCK-8) was used to evaluate cell proliferation, and flow cytometry was used to assess the cell cycle of CD34+CD38− LSCs. The SA-β-Gal staining and CFU-Mix assay were conducted to measure senescence of CD34+CD38− LSCs. The mRNA transcription and protein expression of p16INK4a and human telomerase reverse transcriptase (hTERT) were determined using a real-time polymerase chain reaction (RT-PCR) and western blot assay, respectively. Results. The Rg1 treatment significantly attenuated proliferative activity and decreased the proliferative index (PI) of CD34+CD38− LSCs compared to those of the control group (p < 0.05). It remarkably increased positive SA-β-Gal staining rate, and suppressed formation of the CFU-Mix of CD34+CD38− LSCs compared with those of the control group (p < 0.05). The Rg1 treatment markedly boosted telomere effector, p16INK4a, in CD34+CD38− LSCs compared with that of control group (p < 0.05). Such treatment obviously reduced telomere regulator, hTERT, in CD34+CD38− LSCs compared with the control group (p < 0.05). Conclusions. Ginsenoside Rg1-induced senescence of CD34+CD38− LSCs through upregulating p16INK4a and downregulating hTERT expression, both of which are associated with telomere systems. The present study would be beneficial for the treatment of leukemia by providing a promising strategy to induce senescence of CD34+CD38− LSCs.