The Flavagline Compound 1-(2-(dimethylamino)acetyl)-Rocaglaol Induces Apoptosis in K562 Cells by Regulating the PI3K/Akt/mTOR, JAK2/STAT3, and MAPK Pathways

  • Drug Des Devel Ther. 2022 Aug 4;16:2545-2557. doi: 10.2147/DDDT.S357891.
Xinmei Yang  1  2  3 ,  Xijun Wu  4 ,  Xiaosen Wu  5 ,  Lei Huang  1  2 ,  Jingrui Song  1  2 ,  Chunmao Yuan  1  2 ,  Zhixu He  3  6 ,  Yanmei Li  1  2
Affiliations
  • 1. State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, People's Republic of China.
  • 2. The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guizhou Medical University, Guiyang, 550014, People's Republic of China.
  • 3. Stem Cell and Tissue Engineering Research Center, Guizhou Medical University, Guiyang, 550004, People's Republic of China.
  • 4. Department of Laboratory, The Affiliated Jinyang Hospital of Guizhou Medical University, Guiyang, 550023, People's Republic of China.
  • 5. FuRong Tobacco Research Station, Xiangxi Autonomous Prefecture Tobacco Company Yongshun Branch, Yongshun, 416700, People's Republic of China.
  • 6. Department of Pediatrics, Affiliated Hospital of Guizhou Medical University, Guiyang, 550001, People's Republic of China.
PMID: 35959422 DOI: 10.2147/DDDT.S357891
Abstract

Purpose: Chronic myelogenous leukemia (CML) is a hematological malignancy with increased proliferation of cells of the myeloid series. This can disrupt normal hematopoiesis. The 1-(2-(dimethylamino)acetyl)-rocaglaol (MQ-16) is a new synthetic flavagline compound that showed promising activity in chronic myeloid leukemia K562 cells. This study aims to analyze the underlying mechanisms of MQ-16 against CML.

Methods: Growth, cell cycle progression, and Apoptosis were assessed in K562 cells following MQ-16 exposure by MTT assay and flow cytometry. The effect of MQ-16 on DNA strands between nucleosomes was examined by 1% Agarose gel electrophoresis. PI3K/Akt/mTOR, JAK2/STAT3, and mitogen-activated protein kinase (MAPK) pathway-related proteins were detected in MQ-16-treated K562 cells by Western blot.

Results: MQ-16 significantly inhibited the proliferation of K562 cells and arrested the cell cycle at the G2/M phase in a time- and concentration-dependent manner. MQ-16 induced mitochondria-dependent Apoptosis by downregulating the anti-apoptotic proteins Bcl-2 and Bcl-xL and induced time- and concentration-dependent DNA fragmentation. In addition, MQ-16 affected the expression of PI3K/Akt/mTOR, JAK2/STAT3, and MAPK pathway-related proteins.

Conclusion: In summary, MQ-16 appears to be a promising chemotherapeutic drug for treating CML.

Keywords
CML; JAK2/STAT3; MAPK; PI3K/Akt/mTOR; apoptosis; cycle arrest; flavagline.
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