title: Damnacanthal, a noni component, exhibits antitumorigenic activity in human colorectal cancer cells.
abstract: Damnacanthal, an anthraquinone compound, is isolated from the roots of Morinda citrifolia L. (noni), which has been used for traditional therapy in several chronic diseases including cancer. Although noni has been consumed for a long time in Asian and Polynesian countries, the molecular mechanisms by which it exerts several benefits are starting to emerge. In this report, we examined systematic approaches on the cancer-suppressing capability of damnacanthal in colorectal tumorigenesis. Damnacanthal exhibits cell growth arrest as well as caspase activity induction in colorectal cancer cells. We also examined several potential target proteins and found that the proapoptotic protein nonsteroidal anti-inflammatory activated gene-1 (NAG-1) is highly induced. Subsequently, we have found that damnacanthal also enhances transcription factor CCAAT/enhancer binding protein β (C/EBPβ), which controls NAG-1 transcriptional activity. Blocking of C/EBPβ by shRNA results in the reduction of NAG-1 expression as well as caspase activity in the presence of damnacanthal. Taken together, these results indicate that damnacanthal increases antitumorigenic activity in human colorectal cancer cells and that C/EBPβ plays a role in damnacanthal-induced NAG-1 expression.
authors.affiliation: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996-4542, USA.
authors.forename: Thararat
authors.initials: T
authors.lastname: Nualsanit
authors.forename: Pleumchitt
authors.initials: P
authors.lastname: Rojanapanthu
authors.forename: Wandee
authors.initials: W
authors.lastname: Gritsanapan
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Darunee
authors.initials: D
authors.lastname: Lawson
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Baek
mesh_terms: D000880:Anthraquinones / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D055436:Growth Differentiation Factor 15 / Q000235:genetics / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D032066:Morinda / Q000737:chemistry*
chemical_list: D000880:Anthraquinones; D016588:Anticarcinogenic Agents; D022762:CCAAT-Enhancer-Binding Proteins; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; C079170:damnacanthal