2. Academic Validation
  3. Jujuboside B promotes the death of acute leukemia cell in a RIPK1/RIPK3/MLKL pathway-dependent manner

Jujuboside B promotes the death of acute leukemia cell in a RIPK1/RIPK3/MLKL pathway-dependent manner

  • Eur J Pharmacol. 2020 Jun 5:876:173041. doi: 10.1016/j.ejphar.2020.173041.
Miao-Miao Jia 1,  Yue-Qi Li 1,  Ke-Qian Xu 1,  Yi-Yue Zhang 2,  Shi-Ming Tan 3,  Qin Zhang 3,  Jun Peng 4,  Xiu-Ju Luo 5
Affiliations

Affiliations

  • 1 Department of Laboratory Medicine, The Third Xiangya Hospital of Central South University, Changsha, 410013, China.
  • 2 Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China.
  • 3 Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha, 410013, China.
  • 4 Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China; Hunan Provincial Key Laboratory of Cardiovascular Research, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410078, China.
  • 5 Department of Laboratory Medicine, The Third Xiangya Hospital of Central South University, Changsha, 410013, China. Electronic address: [email protected].
PMID: 32142769 DOI: 10.1016/j.ejphar.2020.173041
Abstract

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.

Keywords

Acute leukemia cell; Jujuboside B; MLKL; Necroptosis; RIPK1; RIPK3.

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