Protein-bound polysaccharide-K (PSK) induces apoptosis via p38 mitogen-activated protein kinase pathway in promyelomonocytic leukemia HL-60 cells

Anticancer Res. 2012 Jul;32(7):2631-7.

Abstract

Background/aim: 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.

Materials and 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.

Conclusion: The p38 MAPK pathway plays an important role in PSK-induced apoptosis.

MeSH terms

  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Differentiation / drug effects
  • Drug Interactions
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology
  • HL-60 Cells
  • Humans
  • Imidazoles / pharmacology
  • Leukemia, Promyelocytic, Acute / drug therapy
  • Leukemia, Promyelocytic, Acute / enzymology
  • Leukemia, Promyelocytic, Acute / pathology
  • MAP Kinase Signaling System / drug effects*
  • Phosphorylation / drug effects
  • Proteoglycans / pharmacology*
  • Pyridines / pharmacology
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Enzyme Inhibitors
  • Imidazoles
  • Proteoglycans
  • Pyridines
  • polysaccharide-K
  • p38 Mitogen-Activated Protein Kinases
  • Caspase 3
  • SB 203580