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International Journal of Oral Science ; (4): 81-89, 2009.
Article in English | WPRIM | ID: wpr-269731

ABSTRACT

<p><b>AIM</b>To investigate the effect of DAPT (gamma-secretase inhibitor) on the growth of human tongue carcinoma cells and to determine the molecular mechanism to enable the potential application of DAPT to the treatment of tongue carcinoma.</p><p><b>METHODOLOGY</b>Human tongue carcinoma Tca8113 cells were cultured with DAPT. Cell growth was determined using Indigotic Reduction method. The cell cycle and apoptosis were analyzed by flow cytometry. Real-time PCR and Immuno-Fluorescence (IF) were employed to determine the intracellular expression levels.</p><p><b>RESULTS</b>DAPT inhibited the growth of human tongue carcinoma Tca8113 cells by inducing G0-G1 cell cycle arrest and apoptosis. The mRNA levels of Hairy/Enhancer of Split-1 (Hes-1), a target of Notch activation, were reduced by DAPT in a dose-dependent manner. Coincident with this observation, DAPT induced a dose-dependent promotion of constitutive Caspase-3 in Tca8113 cells.</p><p><b>CONCLUSION</b>DAPT may have a therapeutic value for human tongue carcinoma. Moreover, the effects of DAPT in tumor inhibition may arise partly via the modulation of Notch-1 and Caspase-3.</p>


Subject(s)
Humans , Amyloid Precursor Protein Secretases , Antineoplastic Agents , Pharmacology , Apoptosis , Basic Helix-Loop-Helix Transcription Factors , Carcinoma , Pathology , Caspase 3 , Cell Line, Tumor , Cell Membrane , Cell Nucleus , Cyclin D1 , Dipeptides , Pharmacology , Dose-Response Relationship, Drug , G1 Phase , Homeodomain Proteins , Receptor, Notch1 , Repressor Proteins , Resting Phase, Cell Cycle , Tongue Neoplasms , Pathology , Transcription Factor HES-1
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