Anti-proliferative properties of kahweol in oral squamous cancer through the regulation specificity protein 1.
Phytother Res. 2014 Dec ;28(12):1879-86. Epub 2014 Sep 8. PMID: 25196544
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.