E35 ablates acute leukemia stem and progenitor cells in vitro and in vivo

Chen, Yingyu; Zheng, Jing; Gan, Donghui; Chen, Yanxin; Zhang, Na; Chen, Yu‐Wen; Lin, Zhenxing; Wang, Wenfeng; Chen, Haijun; Dong, Lin; Hu, Jianda

doi:10.1002/jcp.29457

Cited by 8 publications

(4 citation statements)

References 46 publications

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“…Peripheral whole blood samples were obtained at patients’ scheduled visits after disease diagnosis. Peripheral blood mononuclear cells (PBMCs) were isolated according to the procedures we previously reported ( 24 – 26 ). For platelet preparation, venous blood was obtained by venipuncture into EDTA-based anticoagulant tubes.…”

Section: Methodsmentioning

confidence: 99%

Association of Platelet Desialylation and Circulating Follicular Helper T Cells in Patients With Thrombocytopenia

et al. 2022

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Thrombocytopenia is a multifactorial condition that frequently involves concomitant defects in platelet production and clearance. The physiopathology of low platelet count in thrombocytopenia remains unclear. Sialylation on platelet membrane glycoprotein and follicular helper T cells (TFHs) are thought to be the novel platelet clearance pathways. The aim of this study was to clarify the roles of platelet desialylation and circulating TFHs in patients with immune thrombocytopenia (ITP) and non-ITP thrombocytopenia. We enrolled 190 patients with ITP and 94 patients with non-ITP related thrombocytopenia including case of aplastic anemia (AA) and myelodysplastic syndromes (MDS). One hundred and ten healthy volunteers were included as controls. We found significantly increased desialylated platelets in patients with ITP or thrombocytopenia in the context of AA and MDS. Platelet desialylation was negatively correlated with platelet count. Meanwhile, the circulating TFH levels in patients with thrombocytopenia were significantly higher than those of normal controls, and were positively correlated with desialylated platelet levels. Moreover, TFHs-related chemokine CXCL13 and apoptotic platelet levels were abnormally high in ITP patients. The upregulation of pro-apoptotic proteins and the activation of the MAPK/mTOR pathway were observed in the same cohort. These findings suggested that platelet desialylation and circulating TFHs may become the potential biomarkers for evaluating the disease process associated with thrombocytopenia in patients with ITP and non-ITP.

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Section: Methodsmentioning

confidence: 99%

Association of Platelet Desialylation and Circulating Follicular Helper T Cells in Patients With Thrombocytopenia

et al. 2022

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“…synthesized another class of emodin quaternary ammonium salt derivatives, and identified E35 (BrNO5·H2O) as a potential therapeutic candidate for hematologic cancers with higher aqueous solubility and specificity than emodin. E35 efficiently suppressed growth and enhanced apoptosis of various acute leukemia stem and progenitor cells, including but not limit to HL-60, Molt-4, and CA46, by markedly downregulating the drug-resistant genes like MDR1, MRP1, TOPIIβ , GSTπ, and BCL-2 , and dramatically blocking AKT/mTOR pathway [ 205 ].…”

Section: Modification Of Emodin For Better Therapeutic Potentialmentioning

confidence: 99%

Advances in the study of emodin: an update on pharmacological properties and mechanistic basis

Zheng

et al. 2021

Chin Med

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Rhei Radix et Rhizoma, also known as rhubarb or Da Huang, has been widely used as a spice and as traditional herbal medicine for centuries, and is currently marketed in China as the principal herbs in various prescriptions, such as Da-Huang-Zhe-Chong pills and Da-Huang-Qing-Wei pills. Emodin, a major bioactive anthraquinone derivative extracted from rhubarb, represents multiple health benefits in the treatment of a host of diseases, such as immune-inflammatory abnormality, tumor progression, bacterial or viral infections, and metabolic syndrome. Emerging evidence has made great strides in clarifying the multi-targeting therapeutic mechanisms underlying the efficacious therapeutic potential of emodin, including anti-inflammatory, immunomodulatory, anti-fibrosis, anti-tumor, anti-viral, anti-bacterial, and anti-diabetic properties. This comprehensive review aims to provide an updated summary of recent developments on these pharmacological efficacies and molecular mechanisms of emodin, with a focus on the underlying molecular targets and signaling networks. We also reviewed recent attempts to improve the pharmacokinetic properties and biological activities of emodin by structural modification and novel material-based targeted delivery. In conclusion, emodin still has great potential to become promising therapeutic options to immune and inflammation abnormality, organ fibrosis, common malignancy, pathogenic bacteria or virus infections, and endocrine disease or disorder. Scientifically addressing concerns regarding the poor bioavailability and vague molecular targets would significantly contribute to the widespread acceptance of rhubarb not only as a dietary supplement in food flavorings and colorings but also as a health-promoting TCM in the coming years.

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“…We also found that emodin induces apoptosis in resistant acute leukemia cells [ 7 ]. One emodin derivative, Emodin 35 (E35, C 34 H 50 BrNO 5 ·H 2 O; molecular weight, 631.29; Figure 1(a) ), has been shown to downregulate TP53 protein expression and decrease PI3K/Akt protein phosphorylation in diffused large B cell lymphoma cells [ 8 ] while downstreaming Crk, Akt/mTOR, and MEK/ERK pathways in 32Dp210-T315I leukemia cells [ 9 ], inhibiting the cellular growth, and inducing apoptosis in leukemia cells [ 10 ]. By far, most studies focused on the effects of emodin on leukemia, and only limited studies investigated the effects of emodin on MM.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Investigation of the Cytotoxic Activity of Emodin 35 Derivative on Multiple Myeloma Cell Lines

Zheng

Chen

Zheng

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Bortezomib is used for treating multiple myeloma (MM); however, it has considerable adverse effects. Emodin has been reported to exhibit inhibitory effects on MM cell lines. We investigated the efficacy of emodin 35 (E35), an emodin derivative, using U266 and MM1s cell lines in treating MM and the efficacy of combining bortezomib and E35. Methods. MTT assays were used to observe the effects of E35 on MM cell growth. The effects on cellular apoptosis were then observed using Annexin V/propidium iodide (PI) staining assay. The expression of apoptosis-related genes, including the caspase family, was examined. The efficacy of combining bortezomib and E35 was investigated by examining the expression of the Akt/mTOR/4EBP1 signaling pathway-related proteins. Results. We report that E35 inhibited the growth of U266 and MM1s cells by inducing cellular apoptosis. Moreover, E35 downregulated the expression of apoptosis-related genes and suppressed the phosphorylation of Akt/mTOR/4EBP1 signaling pathway-related genes, thus exhibiting synergistic effects with bortezomib. All observed effects were dose-dependent. Conclusion. The results showed that E35 exhibited cytotoxic effects in MM cell lines in protein levels. Thus, E35, particularly in combination with bortezomib, may be considered as a promising treatment for MM; however, this requires further investigation in vivo.

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E35 ablates acute leukemia stem and progenitor cells in vitro and in vivo

Cited by 8 publications

References 46 publications

Association of Platelet Desialylation and Circulating Follicular Helper T Cells in Patients With Thrombocytopenia

Association of Platelet Desialylation and Circulating Follicular Helper T Cells in Patients With Thrombocytopenia

Advances in the study of emodin: an update on pharmacological properties and mechanistic basis

In Vitro Investigation of the Cytotoxic Activity of Emodin 35 Derivative on Multiple Myeloma Cell Lines

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