DAPT enhances the apoptosis of human tongue carcinoma cells.
- Author:
Brian E GROTTKAU
1
;
Xi-Rui CHEN
;
Claudia C FRIEDRICH
;
Xing-Mei YANG
;
Wei JING
;
Yao WU
;
Xiao-Xiao CAI
;
Yu-Rong LIU
;
Yuan-Ding HUANG
;
Yun-Feng LIN
Author Information
- Publication Type:Journal Article
- MeSH: Amyloid Precursor Protein Secretases; antagonists & inhibitors; Antineoplastic Agents; administration & dosage; pharmacology; Apoptosis; drug effects; Basic Helix-Loop-Helix Transcription Factors; drug effects; Carcinoma; pathology; Caspase 3; drug effects; Cell Line, Tumor; Cell Membrane; drug effects; Cell Nucleus; drug effects; Cyclin D1; drug effects; Dipeptides; administration & dosage; pharmacology; Dose-Response Relationship, Drug; G1 Phase; drug effects; Homeodomain Proteins; drug effects; Humans; Receptor, Notch1; drug effects; Repressor Proteins; drug effects; Resting Phase, Cell Cycle; drug effects; Tongue Neoplasms; pathology; Transcription Factor HES-1
- From: International Journal of Oral Science 2009;1(2):81-89
- CountryChina
- Language:English
-
Abstract:
AIMTo 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.
METHODOLOGYHuman 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.
RESULTSDAPT 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.
CONCLUSIONDAPT 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.
