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Apoptosis in Leukemic Cells Induced by Anti-Proliferative Coumarin Isolated from the Stem Bark of Fraxinus rhynchophylla

  • Lee, Beom Zoo (Department of Food Science and Biotechnology, College of Life Science and Biotechnology, Dongguk University) ;
  • Lee, Ik Soo (Herbal Medicine Research Division, Korea Institute of Oriental Medicine) ;
  • Pham, Chau Ha (Group for Biometrology, Korea Research Institute of Standards and Science (KRISS)) ;
  • Jeong, Soon-Kyu (Chemland Co., Ltd.) ;
  • Lee, Sulhae (Chemland Co., Ltd.) ;
  • Hong, KwangWon (Department of Food Science and Biotechnology, College of Life Science and Biotechnology, Dongguk University) ;
  • Yoo, Hee Min (Group for Biometrology, Korea Research Institute of Standards and Science (KRISS))
  • Received : 2020.06.16
  • Accepted : 2020.07.17
  • Published : 2020.08.28

Abstract

Esculetin 6-O-β-D-arabinofuranosyl-(1 → 6)-β-D-glucopyranoside (EAG) is a coumarin glycoside isolated from the stem bark of Fraxinus rhynchophylla. This study scrutinized the anti-proliferative activity of EAG on blood cancer-derived Jurkat leukemic cells. Cell viability assays in leukemic cancer cells determined that EAG possesses potent anti-proliferative effects. Moreover, treatment with EAG increased the proportion of apoptotic cells, resulted in cell cycle arrest being induced at the subG0/G1 phase, and reduced the proportion of cells present in the S phase. In addition, mitochondrial membrane potential was reduced by EAG in Jurkat cells. Additionally, EAG triggered apoptosis that was mediated by the downregulation of BCL-XL, p-IκBα, and p-p65 expressions in addition to the upregulation of cleaved Caspase 3 and BAX expressions. These findings revealed that the toxic effect of EAG was mediated by intracellular signal transduction pathways that involved a mechanism in which reactive oxygen species (ROS) were upregulated. Thus, this study concludes that EAG could potentially serve as a therapeutic agent for leukemia.

Keywords

References

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