title: Capsaicin represses transcriptional activity of β-catenin in human colorectal cancer cells.
abstract: Capsaicin is a pungent ingredient in chili red peppers and has been linked to suppression of growth in various cancer cells. However, the underlying mechanism(s) by which capsaicin induces growth arrest and apoptosis of cancer cells is not completely understood. In the present study, we investigated whether capsaicin alters β-catenin-dependent signaling in human colorectal cancer cells in vitro. Exposure of SW480, LoVo and HCT-116 cells to capsaicin suppressed cell proliferation. Transient transfection with a β-catenin/T-cell factor (TCF)-responsive reporter indicated that capsaicin suppressed the transcriptional activity of β-catenin/TCF. Capsaicin treatment resulted in a decrease of intracellular β-catenin levels and a reduction of transcripts from the β-catenin gene (CTNNB1). These results were confirmed by a reduced luciferase reporter activity driven by promoter-reporter construct containing the promoter region of the Catnb gene. In addition, capsaicin destabilized β-catenin through enhancement of proteosomal-dependent degradation. Western blot and immunoprecipitation studies indicated that capsaicin treatment suppressed TCF-4 expression and disrupted the interaction of TCF-4 and β-catenin. This study identifies a role for the β-catenin/TCF-dependent pathway that potentially contributes to the anticancer activity of capsaicin in human colorectal cancer cells.
authors.affiliation: Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996-4542, USA. slee27@utk.edu
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Raphael L
authors.initials: RL
authors.lastname: Richardson
authors.forename: Roderick H
authors.initials: RH
authors.lastname: Dashwood
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Baek
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002211:Capsaicin / Q000494:pharmacology*; D002212:Capsicum / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D047468:Immunoprecipitation; D010936:Plant Extracts / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: C495270:CTNNB1 protein, human; D010936:Plant Extracts; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D051176:beta Catenin; D002211:Capsaicin