title: Anti-proliferative properties of kahweol in oral squamous cancer through the regulation specificity protein 1.
abstract: Kahweol, the coffee-specific deterpene, has been shown to have potential anti-cancer effects against several cancers. However, the molecular mechanisms underlying the anti-cancer activity of kahweol have not yet established. In this study, we investigated whether kahweol could show anti-cancer effects on oral squamous cell lines (OSCCs), HN22 and HSC4. We conducted an 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, 4'-6-diamidino2-phenylindole (DAPI) staining, propidium iodide staining, immunocytochemistry, and Western blot analysis for the characterization of kahweol and the underlying signaling pathway. We determined that kahweol-treated cells showed significantly decreased cell viability and increased nuclear condensation and an increased sub-G1 population in OSCCs. Interestingly, suppression of the transcription factor specificity protein 1 (Sp1) was followed by induced apoptosis by kahweol in a dose-dependent manner. In addition, kahweol modulated the protein expression level of the Sp1 regulatory genes including cell cycle regulatory proteins and anti-apoptotic proteins, resulting in apoptosis. Taken together, results from these findings suggest that kahweol may be a potential anti-cancer drug candidate to induce apoptotic cell death through downregulation of Sp1 in OSCCs.
authors.affiliation: Department of Oral Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 plus, Chonbuk National University, Jeonju, 651-756, Korea.
authors.forename: Jung-Il
authors.initials: JI
authors.lastname: Chae
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Jeon
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Shim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation; D006801:Humans; D009062:Mouth Neoplasms / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D016329:Sp1 Transcription Factor / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; C053401:kahweol
keywords: Sp1; apoptosis; coffee; kahweol; oral squamous cancer cell