title: Protein-bound polysaccharide-K (PSK) induces apoptosis via p38 mitogen-activated protein kinase pathway in promyelomonocytic leukemia HL-60 cells.
abstract: OBJECTIVE
  Protein-bound polysaccharide-K (PSK) is extracted from Coriolus versicolor (CM101) and is clinically used in combination therapy for gastrointestinal cancer and small-cell lung carcinoma. We have previously demonstrated that PSK induces apoptosis and inhibites proliferation of promyelomonocytic leukemia HL-60 cells, but the signaling pathway for this action remains to be elucidated. In HL-60 cells, the mitogen-activated protein kinase (MAPK) pathway has been reported to be involved in stimuli-induced apoptosis. Therefore, involvement of the p38 MAPK pathway in PSK-induced apoptosis was herein investigated.
  
  
  METHODS
  HL-60 cells were used in this study. Western blotting was performed to detect phosphorylated p38 MAPK. A p38 MAPK inhibitor, SB203580, was used to examine the roles of p38 MAPK in PSK-induced apoptosis and growth inhibition.
  
  
  RESULTS
  PSK induced p38 MAPK phosphorylation. Co-treatment with SB203580 blocked PSK-induced apoptosis, caspase-3 activation and growth inhibition.
  
  
  CONCLUSIONS
  The p38 MAPK pathway plays an important role in PSK-induced apoptosis.
authors: Department of Digestive and General Surgery, Shimane University Faculty of Medicine, 89-1 Enya-cho, Izumo, Shimane 693-8501, Japan. norinorihirahara@yahoo.co.jp
authors: Noriyuki
authors: N
authors: Hirahara
authors: Takeo
authors: T
authors: Edamatsu
authors: Ayako
authors: A
authors: Fujieda
authors: Masaki
authors: M
authors: Fujioka
authors: Tsutomu
authors: T
authors: Wada
authors: Yoshitsugu
authors: Y
authors: Tajima
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011509:Proteoglycans / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D011509:Proteoglycans; D011725:Pyridines; C010770:polysaccharide-K; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; C093642:SB 203580