title: Anti-proliferative effect of horehound leaf and wild cherry bark extracts on human colorectal cancer cells.
abstract: Marubium vulgare (horehound) and Prunus serotina (wild cherry) have been traditionally used for the treatment of inflammatory-related symptoms such as cold, fever, and sore throat. In this report, we show that extracts of anti-inflammatory horehound leaves and wild cherry bark exhibit anti-proliferative activity in human colorectal cancer cells. Both horehound and wild cherry extracts cause suppression of cell growth as well as induction of apoptosis. We found that horehound extract up-regulates pro-apoptotic non-steroidal anti-inflammatory drug-activated gene (NAG-1) through transactivation of the NAG-1 promoter. In contrast, wild cherry extract decreased cyclin D1 expression and increased NAG-1 expression in HCT-116 and SW480 cell lines. Treatment with wild cherry extract resulted in the suppression of beta-catenin/T cell factor transcription, as assessed by TOP/FOP reporter constructs, suggesting that suppressed beta-catenin signaling by wild cherry extract leads to the reduction of cyclin D1 expression. Our data suggest the mechanisms by which these extracts suppress cell growth and induce apoptosis involve enhanced NAG-1 expression and/or down-regulation of beta-catenin signaling, followed by reduced cyclin D1 expression in human colorectal cancer cells. These findings may provide mechanisms for traditional anti-inflammatory products as cancer chemopreventive agents.
authors.affiliation: Laboratory of Environmental Carcinogenesis, Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, 37996, USA.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Jason L
authors.initials: JL
authors.lastname: Liggett
authors.forename: Nam-Cheol
authors.initials: NC
authors.lastname: Kim
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Baek
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D055436:Growth Differentiation Factor 15; D006801:Humans; D027522:Marrubium; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016588:Anticarcinogenic Agents; D016207:Cytokines; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D010936:Plant Extracts; D051176:beta Catenin; C508337:Marrubium vulgare extract