Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Flavonoids from Orostachys Japonicus A. Berger Induces Caspase-dependent Apoptosis at Least Partly through Activation of p38 MAPK Pathway in U937 Human Leukemic Cells

  • Lee, Won Sup (Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine) ;
  • Yun, Jeong Won (Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine) ;
  • Nagappan, Arulkumar (Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine) ;
  • Jung, Ji Hyun (Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine) ;
  • Yi, Sang Mi (Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine) ;
  • Kim, Dong Hoon (Department of Emergency Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine) ;
  • Kim, Hye Jung (Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University School of Medicine) ;
  • Kim, GonSup (School of Veterinary Medicine, Gyeongsang National University School of Medicine) ;
  • Ryu, Chung Ho (Division of Applied Life Science (BK 21 Program), Institute of Agriculture and Life Science, Gyeongsang National University) ;
  • Shin, Sung Chul (Department of Chemistry, Research Institute of Life Science, Gyeongsang National University) ;
  • Hong, Soon Chan (Department of Surgery, Institute of Health Sciences, Gyeongsang National University School of Medicine) ;
  • Choi, Yung Hyun (Department of Biochemistry, Dongeui University College of Oriental Medicine) ;
  • Jung, Jin-Myung (Department of Neurosurgery, Institute of Health Sciences, Gyeongsang National University School of Medicine)
  • Published : 2015.02.25
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Abstract

Background: Orostachys japonicus A. Berger (A. Berger) is commonly used as a folk remedy for cancer therapy. However, the mechanisms of its anti-cancer activity are poorly investigated in human cancer cells. In this study, we investigated whether flavonoids extracted from Orostachys japonicus A. Berger (FEOJ) might have anticancer effects in human leukemia cells, focusing on cell death mechanisms. Materials and Methods: U937 human leukemic cancer cells were used. Results: FEOJ induced apoptosis in a dose-dependent manner in human U937 cancer cells. Flow cytometry revealed significant accumulation of cells with sub-G1 DNA content at the concentrations of $200{\mu}g/mL$ and $400{\mu}g/mL$. FEOJ-induced apoptosis was caspase-dependent through loss of mitochondrial membrane potential (MMP, ${\Delta}{\Psi}m$) in human U937 cancer cells, which might be associated with suppression of Bcl-2 and XIAP proteins. FEOJ induced the p38 MAPK signaling pathway, playing at least in part an important role in FEOJ-induced apoptosis. Conclusions: This study suggested that FEOJ may induce caspase-dependent apoptosis in human leukemic cells by regulating MMP (${\Delta}{\Psi}m$) through suppressing Bcl-2 and X-IAP. In addition, the results indicated that upstream p38 MAPK signaling regulates the apoptotic effect of FEOJ. This study provides evidence that FEOJ might have anti-cancer potential for human leukemic cells.

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