Capsaicin promotes a more aggressive gene expression phenotype and invasiveness in null-TRPV1 urothelial cancer cells

• Published in: Carcinogenesis (New York) 2011-05, Vol.32 (5), p.686-694
• Main Authors: CAPRODOSSI, Sara, AMANTINI, Consuelo, NABISSI, Massimo, MORELLI, Maria Beatrice, FARFARIELLO, Valerio, SANTONI, Matteo, GISMONDI, Angela, SANTONI, Giorgio
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Blotting, Western; Calcium - metabolism; Capsaicin - pharmacology; Carcinogenesis, carcinogens and anticarcinogens; Carcinoma, Papillary - genetics; Carcinoma, Papillary - pathology; Cell Adhesion - drug effects; Cell Line; Cell Movement - drug effects; Cell Proliferation - drug effects; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Fluorescent Antibody Technique; Gene Expression - drug effects; Gene Expression Profiling; Humans; Lymphocytes, Null; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Medical sciences; Oligonucleotide Array Sequence Analysis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Sensory System Agents - pharmacology; Signal Transduction; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism; Tumors; Urologic Neoplasms - genetics; Urologic Neoplasms - pathology; Urothelium - metabolism
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgr025

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.