title: Capsaicin promotes a more aggressive gene expression phenotype and invasiveness in null-TRPV1 urothelial cancer cells.
abstract: Capsaicin (CPS) has been found to exhibit either tumor promoting or suppressing effects, many of which are mediated by the specific transient receptor potential vanilloid type-1 (TRPV1). Herein, we provide evidence that CPS treatment induced a more aggressive gene phenotype and invasiveness in 5637 cells-lacking TRPV1 receptor. CPS treatment of 5637 cells induced upregulation of pro-angiogenetic (angiopoietin 1, angiopoietin 2 and vascular endothelial growth factor), pro-invasive and pro-metastatic genes (MMP1, MMP9, TIMP1, TIMP3, granzyme A (GZMA), NM23A and S100A) with a downregulation of apoptotic genes (Fas/CD95 and tumor necrosis factor receptor superfamily member 1A). CPS increased the invasiveness of 5637 cells by triggering IGF (insulin-like growth factor)-1 release, GZMA and MMP9 activation, α-tubulin disassembly and cytoskeleton degradation. Finally, in order to evaluate the relationship between the lack of TRPV1 expression and increased CPS-induced invasiveness, we transfected 5637 cells with the TRPV1 complementary DNA (cDNA) sequence. We found that TRPV1-expressing cells show CPS-mediated calcium level increase, growth inhibition and apoptosis. Moreover, CPS-induced migration and MMP9 activation were reverted, suggesting an inhibitory role played by TRPV1 in urothelial cancer cell invasion and metastasis.
authors.affiliation: School of Pharmacy, Section of Experimental Medicine, University of Camerino, Via Madonna delle carceri 9, Camerino, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Caprodossi
authors.forename: Consuelo
authors.initials: C
authors.lastname: Amantini
authors.forename: Massimo
authors.initials: M
authors.lastname: Nabissi
authors.forename: Maria Beatrice
authors.initials: MB
authors.lastname: Morelli
authors.forename: Valerio
authors.initials: V
authors.lastname: Farfariello
authors.forename: Matteo
authors.initials: M
authors.lastname: Santoni
authors.forename: Angela
authors.initials: A
authors.lastname: Gismondi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Santoni
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D008215:Lymphocytes, Null; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018689:Sensory System Agents / Q000494:pharmacology; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000235:genetics* / Q000378:metabolism; D014571:Urologic Neoplasms / Q000235:genetics / Q000473:pathology*; D019459:Urothelium / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D018689:Sensory System Agents; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D020780:Matrix Metalloproteinase 9; D002211:Capsaicin; D002118:Calcium