title: Blockage of STAT3 Signaling Pathway by Morusin Induces Apoptosis and Inhibits Invasion in Human Pancreatic Tumor Cells.
abstract: OBJECTIVE
  Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor implicated in carcinogenesis. Here, we investigated the role of morusin, the major prenylflavonoid, isolated from Chinese herbal medicine in abrogating the constitutive STAT3 activation in human pancreatic tumor cells.
  
  
  METHODS
  The effect of morusin on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation, and apoptosis was examined.
  
  
  RESULTS
  Morusin specifically inhibited constitutive STAT3 activation both at tyrosine residue 705 and serine residue 727 in 4 pancreatic tumor cells. The inhibition of STAT3 was mediated through the suppression of activation of upstream JAK1, JAK2, and c-Src kinases. Morusin led to the accumulation of the cells in different phases of the cell cycle and caused induction of apoptosis and loss of mitochondrial membrane potential. Morusin downregulated the expression of various STAT3-regulated gene products; this correlated with induction of caspase-3 activation and anti-invasive effects. Treatment with the protein tyrosine phosphatase inhibitor pervanadate reversed the morusin-induced downregulation of STAT3, thereby suggesting the involvement of a protein tyrosine phosphatase.
  
  
  CONCLUSIONS
  Morusin is a novel blocker of STAT3 activation and thus may have potential in negative regulation of growth and metastasis of pancreatic tumor cells.
authors.affiliation: From the College of Korean Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Chulwon
authors.initials: C
authors.lastname: Kim
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Oh
authors.forename: Dongwoo
authors.initials: D
authors.lastname: Nam
authors.forename: Seok Geun
authors.initials: SG
authors.lastname: Lee
authors.forename: Junhee
authors.initials: J
authors.lastname: Lee
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Bum Sang
authors.initials: BS
authors.lastname: Shim
authors.forename: Kwang Seok
authors.initials: KS
authors.lastname: Ahn
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D000081247:CSK Tyrosine-Protein Kinase; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053613:Janus Kinase 1 / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D005419:Flavonoids; D050796:STAT3 Transcription Factor; C057451:morusin; D000081247:CSK Tyrosine-Protein Kinase; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D019061:src-Family Kinases; C000631346:CSK protein, human; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D053148:Caspase 3