title: Curcumin targets fibroblast-tumor cell interactions in oral squamous cell carcinoma.
abstract: Co-culture of periodontal ligament fibroblasts (PDLs) and SCC-25 oral squamous carcinoma cells (OSCC) results in conversion of PDLs into carcinoma-associated fibroblasts (CAFs) and induces epithelial-to mesenchymal transition (EMT) of OSCC tumor cells. We hypothesized that Curcumin targets this dynamic mutual interaction between CAFs and tumor cells. Normal and 2 μM Curcumin-treated co-culture were performed for 4 days, followed by analysis of tumor cell invasivity, mRNA/protein expression of EMT-markers and mediators, activity measure of matrix metalloproteinase 9 (MMP-9), and western blot analysis of signal transduction in tumor cells and fibroblasts. In Curcumin-treated co-culture, in tumor cells, the levels of nuclear factor κB (NFκBα) and early response kinase (ERK)-decreased, in fibroblasts, integrin αv protein synthesis decreased compared to corresponding cells in normal co-culture. The signal modulatory changes induced by Curcumin caused decreased release of EMT-mediators in CAFs and reversal of EMT in tumor cells, which was associated with decreased invasion. These data confirm the palliative potential of Curcumin in clinical application.
authors.affiliation: Department of Otorhinolaryngology and Head and Neck Surgery, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck, Austria. jozsef.dudas@i-med.ac.at
authors.forename: József
authors.initials: J
authors.lastname: Dudás
authors.forename: Alexandra
authors.initials: A
authors.lastname: Fullár
authors.forename: Angela
authors.initials: A
authors.lastname: Romani
authors.forename: Christian
authors.initials: C
authors.lastname: Pritz
authors.forename: Ilona
authors.initials: I
authors.lastname: Kovalszky
authors.forename: Volker
authors.initials: V
authors.lastname: Hans Schartinger
authors.forename: Georg
authors.initials: G
authors.lastname: Mathias Sprinzl
authors.forename: Herbert
authors.initials: H
authors.lastname: Riechelmann
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication / Q000187:drug effects*; D018920:Coculture Techniques / Q000379:methods; D003474:Curcumin / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D010513:Periodontal Ligament / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor; D039564:Integrin alphaV; D016328:NF-kappa B; D012333:RNA, Messenger; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D003474:Curcumin