Huang Qi Huai Granules Induce Apoptosis in Acute Lymphoblastic Leukemia Cells through the Akt/FoxO1 Pathway

Han, Juan; Lin, Meng; Zeng, Dongfeng; Zhang, Zhiquan; Jin, Runming; Zhou, Fen

doi:10.1159/000443119

Cited by 6 publications

(4 citation statements)

References 39 publications

(58 reference statements)

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“…New targets and therapy strategies against leukemia are still of intense interest [40-42]. Zinc plays dual roles in regulating cell proliferation and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Zinc Depletion by TPEN Induces Apoptosis in Human Acute Promyelocytic NB4 Cells

Zhu

Wang

Zhou

et al. 2017

Cell Physiol Biochem

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Background/Aims: The effects of zinc signaling on proliferation or apoptosis of leukemia cells remain elusive. In the present study, we used N, N, N’, N’-tetrakis-(2-pyridylmethyl)-ethylene-diamine (TPEN), a membrane-permeable zinc chelator, to evaluate the effect of zinc depletion on survival and apoptosis of NB4 acute promyelocytic leukemia (APL) cells. Methods: The pro-apoptotic effects of TPEN on NB4 cells were examined by flow cytometry, and observed using an optical microscope. Intracellular labile zinc, nitric oxide (NO) or reactive oxygen species (ROS) changes caused by TPEN were measured by flow cytometry. We then explored possible roles of the crosstalk between intracellular labile zinc signaling and nitric oxide signaling in TPEN-triggered apoptosis. Results: we found that TPEN induced apoptosis in NB4 APL cells in a dosage-dependent manner. We further demonstrated that TPEN triggered apoptosis by attenuating intracellular zinc and nitric oxide signaling in NB4 cells. Both exogenous zinc supplement and the nitric donor sodium nitroprusside (SNP) pre-incubation reversed TPEN-mediated inhibition of intracellular NO and Zn²⁺ signaling, and rescued NB4 cells from apoptosis. Conclusion: These results suggest for the first time that crosstalk between zinc signaling and nitric oxide pathway is essential for the survival of NB4 cells. TPEN induces apoptosis in NB4 cells via negatively regulating intracellular NO and Zn²⁺ signaling. Our in vitro data suggest that zinc depletion by TPEN may be a potential therapeutic strategy for APL.

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“…New targets and therapy strategies against leukemia are still of intense interest [40-42]. Zinc plays dual roles in regulating cell proliferation and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Zinc Depletion by TPEN Induces Apoptosis in Human Acute Promyelocytic NB4 Cells

Zhu

Wang

Zhou

et al. 2017

Cell Physiol Biochem

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“…The following formula was used to calculate the viability ratio of ALL cells. Viability ratio=[(absorbance of experimental group-absorbance of blank group)/(absorbance of untreated group-absorbance of blank group)]×100% [23]. Each experiment was repeated for 3 times.…”

Section: Cell Viability Assaymentioning

confidence: 99%

“…Huaier has been used in TCM for ~1600 years [13]. Studies have shown that Huaier extract exhibits anti-tumor effects in a number of solid tumors [14][15][16][17][18][19][20][21][22], and according to recent reports, HQH induces apoptosis in ALL cells [23]. However, whether HQH exhibits a synergistic effect with glucocorticoids when used to treat ALL remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Huai Qi Huang Potentiates Dexamethasone-Mediated Lethality in Acute Lymphoblastic Leukemia Cells by Upregulating Glucocorticoid Receptor α

Jin

2020

Med Sci Monit

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Background:Glucocorticoids are important components of a number of chemotherapeutic regimens used to treat pediatric acute lymphoblastic leukemia (ALL). A primary cause of treatment failure of ALL is acquired resistance to glucocorticoids. Recently, traditional Chinese medicines were effectively used to treat solid tumors. Thus, the aim of this study was to investigate whether Huai Qi Huang (HQH), a traditional Chinese medicine, increased the efficacy of glucocorticoids in the treatment of ALL, and if so, to determine the underlying mechanism. Material/Methods:Various concentrations of HQH were used to treat Jurkat and Nalm-6 cells for 24 to 72 hours. Subsequently, cells were co-treated with HQH and the glucocorticoid receptor agonist, dexamethasone (DEX), or a MEK inhibitor (PD98059) to verify the synergistic effects on apoptosis in Jurkat and Nalm-6 cells for 24 hours. Cell Counting Kit-8 assay and flow cytometry were used to measure cell viability and apoptosis, respectively. Protein and mRNA expression levels were assessed using western blotting and quantitative polymerase chain reaction. Results:The results revealed that cell survival was reduced and apoptosis was increased as the HQH concentration was increased, and this was accompanied with increases in the levels of BAX, cleaved-caspase-3 and glucocorticoid receptor a (GRa) and decreases in the levels of Bcl-2 and phospho-ERK (pERK). Glucocorticoid receptor b (GRb) and total ERK (t-ERK) had no significant changes. Combined treatment with HQH and DEX or PD98059 increased apoptosis in Jurkat and Nalm-6 cells, and concurrently increased BAX, cleaved-caspase-3, GILZ, NFKBIA, and GRa and decreased Bcl-2 and pERK. Conclusions:HQH enhanced the sensitivity of ALL cells to glucocorticoids by increasing the expression of GRa and inhibiting the MEK/ERK pathway, thus providing a rational foundation for the treatment of ALL with HQH.

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“…Knockdown of the SLC7A7 gene increased the apoptosis rate of Jurkat cells. The possible signaling pathway is as follows: depletion of SLC7A7 disables transport systems that transport cationic amino acids out of the cell, increasing the amount of intracellular cationic amino acids, which can activate mTOR and contribute to apoptosis [30,31]. mTOR activation initiates the mitochondrial pathway of apoptosis and leads to phosphorylation of its downstream effector 4E-BP.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Function of SLC7A7 in T-Cell Acute Lymphoblastic Leukemia

Yang

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Y+LAT1 protein, encoded by the SLC7A7 gene (a member of the SLC7 family), forms the cationic amino acid transport system y+L (system y+L). This system transports cationic amino acids such as arginine and lysine out of the cell. Arginine, in particular, is critical for T-cell activation and function in the immune response. Methods: We analyzed the role of the SLC7A7 gene in the cellular activities of Jurkat cells, specifically the cell cycle and cell proliferation, apoptosis, migration, and invasion. Cell proliferation was assessed using the Cell Counting Kit-8. Apoptosis and the cell cycle were determined with a FACSCalibur flow cytometer. A Transwell chamber was used to measure cell invasion and migration. Results: The proliferative ability of Jurkat cells was not significantly altered by transfection with SLC7A7 overexpression vectors. However, SLC7A7 overexpression significantly decreased the percentage of apoptotic Jurkat cells (P = 0.007) but significantly increased the proportion of G1 phase cells (P = 0.029) and cell migration (P < 0.001) and invasion (P < 0.001). Knockdown of SLC7A7 increased the cell apoptosis rate (P = 0.006) but decreased the G1 phase ratio (P = 0.002) and cell migration (P < 0.001) and invasion (P < 0.001). Conclusions: SLC7A7 plays a significant role in the pathogenesis of T-cell acute lymphoblastic leukemia.

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Huang Qi Huai Granules Induce Apoptosis in Acute Lymphoblastic Leukemia Cells through the Akt/FoxO1 Pathway

Cited by 6 publications

References 39 publications

Zinc Depletion by TPEN Induces Apoptosis in Human Acute Promyelocytic NB4 Cells

Zinc Depletion by TPEN Induces Apoptosis in Human Acute Promyelocytic NB4 Cells

Huai Qi Huang Potentiates Dexamethasone-Mediated Lethality in Acute Lymphoblastic Leukemia Cells by Upregulating Glucocorticoid Receptor α

Function of SLC7A7 in T-Cell Acute Lymphoblastic Leukemia

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