title: In vitro treatment of carcinoma cell lines with pancreatic (pro)enzymes suppresses the EMT programme and promotes cell differentiation.
abstract: BACKGROUND
  Previous research has suggested a putative utility of pancreatic (pro)enzymes in cancer treatment. The aim of the present study was to investigate the in vitro effects of a mixture of two pancreatic pro-enzymes, i.e., Chymotrypsinogen and Trypsinogen, and the enzyme Amylase on three human cancer cell lines, i.e., OE33 (derived from an oesophageal carcinoma), Panc1 (derived from a pancreatic carcinoma) and Caco-2 (derived from a colon carcinoma).
  
  
  RESULTS
  After treatment of the three cancer cell lines with different doses of the (pro)enzymes for up to 7 days, we observed (i) growth inhibition in a dose-dependent manner, (ii) enhanced expression of β-catenin and E-cadherin and decreased expression of several epithelial-mesenchymal transition (EMT)-associated genes, such as Vimentin, Snail and Slug, (iii) differentiation of Caco-2 cells, including the appearance of cell-specific differentiated structures such as microvilli and tight junctions, the acquisition of a more regular polygonal morphology, and an increased expression of the intestinal differentiation markers alkaline phosphatase and cytokeratin 8, and (iv) differentiation of Panc1 cells, including the formation of cell aggregates, an increment on lamellar bodies and an increased expression of the pancreatic differentiation markers glucagon and insulin.
  
  
  CONCLUSIONS
  Our results show that the treatment of three different human cancer cell lines with pancreatic (pro)enzymes results in an enhancement of cell adhesion, an attenuation of several EMT-associated markers, and an increase in the expression of several differentiation-associated markers, suggesting the acquisition of a less malignant phenotype and a decrease in proliferative capacity due to lineage-specific cellular differentiation.
authors.affiliation: Centre for Regenerative Medicine, Department of Biology & Biochemistry, University of Bath, Bath, UK. mperan@ujaen.es
authors.forename: Macarena
authors.initials: M
authors.lastname: Perán
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Marchal
authors.forename: Maria A
authors.initials: MA
authors.lastname: García
authors.forename: Julian
authors.initials: J
authors.lastname: Kenyon
authors.forename: David
authors.initials: D
authors.lastname: Tosh
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000681:Amylases / Q000494:pharmacology; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D018938:Caco-2 Cells; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002919:Chymotrypsinogen / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D053533:Keratin-8 / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014362:Trypsinogen / Q000494:pharmacology*; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D053533:Keratin-8; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014746:Vimentin; D051176:beta Catenin; D014362:Trypsinogen; D002919:Chymotrypsinogen; D000469:Alkaline Phosphatase; D000681:Amylases