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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.
AuthorsJung-Il Chae, Young-Joo Jeon, Jung-Hyun Shim
JournalPhytotherapy research : PTR (Phytother Res) Vol. 28 Issue 12 Pg. 1879-86 (Dec 2014) ISSN: 1099-1573 [Electronic] England
PMID25196544 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 John Wiley & Sons, Ltd.
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Diterpenes
  • Sp1 Transcription Factor
  • Sp1 protein, human
  • kahweol
Topics
  • Antineoplastic Agents, Phytogenic (pharmacology)
  • Apoptosis (drug effects)
  • Carcinoma, Squamous Cell (pathology)
  • Cell Line, Tumor (drug effects)
  • Cell Proliferation (drug effects)
  • Cell Survival (drug effects)
  • Diterpenes (pharmacology)
  • Down-Regulation
  • Humans
  • Mouth Neoplasms (pathology)
  • Signal Transduction (drug effects)
  • Sp1 Transcription Factor (metabolism)

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