title: Flavonoids from Orostachys japonicus A. Berger induces caspase-dependent apoptosis at least partly through activation of p38 MAPK pathway in U937 human leukemic cells.
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.
  
  
  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 μg/mL and 400 μg/mL. FEOJ-induced apoptosis was caspase-dependent through loss of mitochondrial membrane potential (MMP, ΔΨm) 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 (ΔΨm) 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.
authors: Departments of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Korea E-mail : lwshmo@hanmail.net, lwshmo@gshp.gsnu.ac.kr.
authors: Won Sup
authors: WS
authors: Lee
authors: Jeong Won
authors: JW
authors: Yun
authors: Arulkumar
authors: A
authors: Nagappan
authors: Ji Hyun
authors: JH
authors: Jung
authors: Sang Mi
authors: SM
authors: Yi
authors: Dong Hoon
authors: DH
authors: Kim
authors: Hye Jung
authors: HJ
authors: Kim
authors: GonSup
authors: G
authors: Kim
authors: Chung Ho
authors: CH
authors: Ryu
authors: Sung Chul
authors: SC
authors: Shin
authors: Soon Chan
authors: SC
authors: Hong
authors: Yung Hyun
authors: YH
authors: Choi
authors: Jin-Myung
authors: JM
authors: Jung
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D029627:Crassulaceae / Q000737:chemistry*; D005419:Flavonoids / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D005419:Flavonoids; D010936:Plant Extracts; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases