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

Tang, Yanting; Zhang, Chenggui; Liu, Heng; Zhou, Yue; Wang, Yaping; Li, Yuan; Han, Yang; Wang, Cuili

doi:10.12659/msm.918207

Cited by 21 publications

(19 citation statements)

References 39 publications

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“…Pre-labeled EV-rich fractions (75 × 10^12/mL) were incubated with PK1 cells for 48 h, and tracked to confirm engraftment. Staining for SA-Spider-ß-Gal in PK1 cells was performed as previously described [22] following manufacturer's protocol (Cat#SG04-01, Dojindo).…”

Section: In Vitro Ev Efficacymentioning

confidence: 99%

Metabolic syndrome increases senescence-associated micro-RNAs in extracellular vesicles derived from swine and human mesenchymal stem/stromal cells

Meng

Zhu

et al. 2020

Cell Commun Signal

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Background The metabolic syndrome (MetS) is a combination of cardiovascular risk-factors, including obesity, hypertension, hyperglycemia, and insulin resistance. MetS may induce senescence in mesenchymal stem/stromal cells (MSC) and impact their micro-RNA (miRNA) content. We hypothesized that MetS also alters senescence-associated (SA) miRNAs in MSC-derived extracellular vesicles (EVs), and interferes with their function. Methods EVs were collected from abdominal adipose tissue-derived MSCs from pigs with diet-induced MetS or Lean controls (n = 6 each), and from patients with MetS (n = 4) or age-matched Lean controls (n = 5). MiRNA sequencing was performed to identify dysregulated miRNAs in these EVs, and gene ontology to analyze their SA-genes targeted by dysregulated miRNAs. To test for EV function, MetS and Lean pig-EVs were co-incubated with renal tubular cells in-vitro or injected into pigs with renovascular disease (RVD, n = 6 each) in-vivo. SA-b-Galactosidase and trichrome staining evaluated cellular senescence and fibrosis, respectively. Results Both humans and pigs with MetS showed obesity, hypertension, and hyperglycemia/insulin resistance. In MetS pigs, several upregulated and downregulated miRNAs targeted 5768 genes in MSC-EVs, 68 of which were SA. In MetS patients, downregulated and upregulated miRNAs targeted 131 SA-genes, 57 of which overlapped with pig-EVs miRNA targets. In-vitro, MetS-MSC-EVs induced greater senescence in renal tubular cells than Lean-MSC-EVs. In-vivo, Lean-MSC-EVs attenuated renal senescence, fibrosis, and dysfunction more effectively than MetS-MSC-EVs. Conclusions MetS upregulates SA-miRNAs in swine MSC-EVs, which is conserved in human subjects, and attenuates their ability to blunt cellular senescence and repair injured target organs. These alterations need to be considered when designing therapeutic regenerative approaches. Graphical abstract

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Section: In Vitro Ev Efficacymentioning

confidence: 99%

Metabolic syndrome increases senescence-associated micro-RNAs in extracellular vesicles derived from swine and human mesenchymal stem/stromal cells

Meng

Zhu

et al. 2020

Cell Commun Signal

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“…In our previous study, using H 2 O 2 to induce human dermal fibroblasts cells to establish a cell injury model found that the expression of P16, P21, P53, and Caspase‐3 was significantly inhibited, while the signal‐regulated kinase and Akt serine/threonine kinase 1 were activated. This indicates that TFPS can reduce the oxidative stress response and apoptosis rate of model cells by up‐regulating the expression of SIRT1 11 …”

Section: Discussionmentioning

confidence: 90%

Tremellafuciformis polysaccharides inhibit UVA‐induced photodamage of human dermal fibroblast cells by activating up‐regulating Nrf2/Keap1 pathways

You

Zhao

et al. 2021

J of Cosmetic Dermatology

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It is well known that exposure to sunlight is the main cause of oxidative stress in human dermal fibroblasts cells. UVA radiation (320-400 nm) can increase the production of reactive oxygen species (ROS) in cells. By reducing the content of ROS, some active enzyme substances with various antioxidant effects can affect oxidative stress. 1 The enzyme antioxidant system mainly includes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase

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“…We found that Rg1 treatment remarkably attenuated CD34 + CD38 − LSCs proliferation and obviously decreased proliferative index (PI) by modulating cell cycle, which is consistent with the findings of previous studies. 1,28 Therefore, the Rg1 significantly inhibits the proliferation and blocks the cell cycle of CD34 + CD38 − LSCs. The previous study 29 reported that SA-β-Gal staining could reflect the senescence of CD34 + CD38 − LSCs.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, the colony formation assay was carried out as described in previous studies, with some modifications. 1,17 Briefly, the CD34 + CD38 − LSCs were seeded onto 96-well plates, cultured and incubated with methylcellulose (final concentration of 0.8%; Sigma-Aldrich) with 5% CO 2 at 37°C for 2 weeks. A total of 50 or more colony formation units (CFU) of cells were defined as 1 mixed CFU (CFU-Mix).…”

Section: Colony Formation Assaymentioning

confidence: 99%

“…Leukemic stem cells (LSCs), important pathogenic factors of leukemia, play an important role in the initiation of leukemia. 1,2 The clinical recurrence or relapse of leukemia is correlated with decreased therapeutic response for LSCs. 3 Strong resistance of LSCs to traditional, cell cycle-dependent drugs, it leads to a poor therapeutic effect, easy recurrence and drug resistance.…”

Section: Introductionmentioning

confidence: 99%

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

Tang¹,

Wang²,

Zhou³

et al. 2021

Adv Clin Exp Med

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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 senescenceassociated β-galactosidase (SA-β-Gal) staining and CFU-Mix assay were conducted to measure senescence of CD34 + CD38 − LSCs. The mRNA transcription and protein expression of p16 INK4a 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, p16 INK4a , 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 p16 INK4a 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.

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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

Cited by 21 publications

References 39 publications

Metabolic syndrome increases senescence-associated micro-RNAs in extracellular vesicles derived from swine and human mesenchymal stem/stromal cells

Metabolic syndrome increases senescence-associated micro-RNAs in extracellular vesicles derived from swine and human mesenchymal stem/stromal cells

Tremellafuciformis polysaccharides inhibit UVA‐induced photodamage of human dermal fibroblast cells by activating up‐regulating Nrf2/Keap1 pathways

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

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