title: Polysaccharide-K (PSK) increases p21(WAF/Cip1) and promotes apoptosis in pancreatic cancer cells.
abstract: BACKGROUND
  Polysaccharide-K (PSK, Krestin(®)) is a natural remedy and one of the most commonly used medicinal mushroom extracts. It has been used as oral adjuvant treatment in cancer therapy in Japan and other Asian countries for more than 40 years. PSK is thought to be an immune modulator, however, its antitumor actions remain undefined. The aim of the present study was to investigate underlying mechanisms by which PSK exerts its antitumor effects on malignant epithelial cells.
  
  
  METHODS
  Antitumor activities of PSK were evaluated on multiple human pancreatic adenocarcinoma cells in vitro. Cell viability, apoptotic pathways, cytokine expression and involvement of TLR2 and TLR4 were monitored by MTT, flow cytometry, Western blotting and protein arrays.
  
  
  RESULTS
  We demonstrate that PSK acts as a growth inhibitor for pancreatic cancer cells, known otherwise to be highly resistant to conventional chemotherapies. Pancreatic cancer cells can be protected against PSK-mediated growth inhibition by neutralizing antibodies against TLR2 and TLR4. The antiproliferative actions were associated with upregulated cell cycle regulatory p21(WAF/Cip1) and pro-apoptotic protein Bax levels, resulting in cell cycle arrest and induction of apoptosis. In addition, a significant growth inhibition and additive effect was observed with PSK and gemcitabine administered as combined treatment.
  
  
  CONCLUSIONS
  While previous studies have emphasized the potential importance of PSK in immune activation, the present results uncover additional mechanisms on epithelial cells that may contribute to the antitumor effects provided by PSK as suggested by clinical observations.
authors.affiliation: Department of Surgery, Clinical Sciences, Lund University, SE-221 84 Lund, Sweden.
authors.forename: Ann H
authors.initials: AH
authors.lastname: Rosendahl
authors.forename: Chen
authors.initials: C
authors.lastname: Sun
authors.forename: DeQuan
authors.initials: D
authors.lastname: Wu
authors.forename: Roland
authors.initials: R
authors.lastname: Andersson
mesh_terms: D000276:Adjuvants, Immunologic; D000363:Agaricales / Q000737:chemistry; D000903:Antibiotics, Antineoplastic; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011509:Proteoglycans / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000093542:Gemcitabine
chemical_list: D000276:Adjuvants, Immunologic; D000903:Antibiotics, Antineoplastic; D057134:Antibodies, Neutralizing; D018925:Chemokines; D050759:Cyclin-Dependent Kinase Inhibitor p21; D011509:Proteoglycans; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051028:bcl-2-Associated X Protein; D003841:Deoxycytidine; C010770:polysaccharide-K; D000093542:Gemcitabine