Jujuboside B promotes the death of acute leukemia cell in a RIPK1/RIPK3/MLKL pathway-dependent manner
| Autor: | Yue-Qi Li, Ke-Qian Xu, Jun Peng, Shi-Ming Tan, Xiu-Ju Luo, Yi-Yue Zhang, Qin Zhang, Miao-Miao Jia |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cell Survival Necroptosis Cell HL-60 Cells Jurkat Cells 03 medical and health sciences RIPK1 0302 clinical medicine medicine Humans Clonogenic assay Tumor Stem Cell Assay Pharmacology Acute leukemia Chemistry Cell growth Ziziphus U937 Cells Saponins medicine.disease Antineoplastic Agents Phytogenic Leukemia 030104 developmental biology medicine.anatomical_structure Apoptosis Receptor-Interacting Protein Serine-Threonine Kinases Seeds Cancer research Protein Kinases 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | European Journal of Pharmacology. 876:173041 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2020.173041 |
| Popis: | Initiation of necroptosis has been considered as a promising strategy for anticancer therapies, especially for eradicating apoptosis-resistant malignant cells. Jujubisode B is a natural saponins extracted from the seeds of Zizyphi Spinosi Semen, and possesses multiple pharmacological activities, including antianxiety, anti-inflammation, antiplatelet aggregation and induction of apoptosis. This study aims to explore the effect of jujuboside B on acute leukemic cells and the underlying mechanisms. Our results showed that jujuboside B inhibited leukemia cell growth in a dose-dependent manner and attenuated the clonogenic ability of U937 cells, concomitant with activation of RIPK1/RIPK3/MLKL pathway; these phenomena were evidently blocked by necroptosis inhibitor (Nec-1). With the help of Molecular Operating Environment (MOE) program, we identified that RIPK1, RIPK3 and MLKL are potential targets of jujuboside B. To the best of our knowledge, this is the first study to provide evidence that jujuboside B possesses antileukemic activity via a mechanism involving activation of RIPK1/RIPK3/MLKL pathway. |
| Databáze: | OpenAIRE |
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