DAPT enhances the apoptosis of human tongue carcinoma cells.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Grottkau
Brian E
BE
Department of Orthopaedic Surgery, Mass General Hospital for Children, Pediatric Orthopaedic Laboratory for Tissue Engineering, Harvard Medical School, Boston, USA.
Chen
Xi-Rui
XR
Friedrich
Claudia C
CC
Yang
Xing-Mei
XM
Jing
Wei
W
Wu
Yao
Y
Cai
Xiao-Xiao
XX
Liu
Yu-Rong
YR
Huang
Yuan-Ding
YD
Lin
Yun-Feng
YF
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051792:Basic Helix-Loop-Helix Proteins / Q000187:drug effects; D002277:Carcinoma / Q000473:pathology*; D053148:Caspase 3 / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D019938:Cyclin D1 / Q000187:drug effects; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016193:G1 Phase / Q000187:drug effects; D018398:Homeodomain Proteins / Q000187:drug effects; D006801:Humans; D051881:Receptor, Notch1 / Q000187:drug effects; D012097:Repressor Proteins / Q000187:drug effects; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D014062:Tongue Neoplasms / Q000473:pathology*; D000072056:Transcription Factor HES-1
D053829:Amyloid Precursor Protein Secretases; D000970:Antineoplastic Agents; D051792:Basic Helix-Loop-Helix Proteins; D053148:Caspase 3; D019938:Cyclin D1; D004151:Dipeptides; D018398:Homeodomain Proteins; D051881:Receptor, Notch1; D012097:Repressor Proteins; D000072056:Transcription Factor HES-1; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; C497761:NOTCH1 protein, human; C078493:HES1 protein, human