β-Phenethyl isothiocyanate induces death receptor 5 to induce apoptosis in human oral cancer cells via p38.
OBJECTIVE
β-Phenylethyl isothiocyanate (PEITC) has been demonstrated to fight many types of cancers through various molecular pathways. In this study, we focused on its effect on the induction of apoptosis to inhibit cell growth and molecular mechanism in oral cancer.


METHODS
3-(4,5-dimethylthiazol-2-yl)-5-(2,4-disulfophenyl)-2-(4 sulfophenyl)-2H-tetrazolium (MTS) assay was used to examine cell viability. The apoptotic effect was investigated using 4'-6-Diamidino-2-phenylindole (DAPI) staining or Western blotting. Inhibitors were used to determine the molecular target and mechanism of PEITC-mediated apoptosis.


RESULTS
β-Phenylethyl isothiocyanate inhibited the growth of HN22 human oral cancer cells and induced caspase-dependent apoptosis in HN22 cells as evidenced by nuclear fragmentation and the activation of caspase 3. It increased cleaved caspase 8, truncated BID, and death receptor 5 (DR5) through the activation of p38 MAPK. This result was confirmed by blockage of PEITC-induced cleavages of Poly(ADP-ribose) Polymerase, caspase-3, caspase-8, and DR5 by p38 MAPK inhibitor, SB203580. We also found that PEITC activated p38 and augmented DR5 to induce apoptosis in other human oral cancer cells.


CONCLUSIONS
These results suggest that DR5 is a potential molecular target for PEITC-induced apoptosis in oral cancer via p38 MAPK.
Department of Oral Pathology, School of Dentistry, Institute of Oral Bioscience, Brain Korea 21, Chonbuk National University, Jeonju, Jeonju, Korea.
L D
LD
Huong
J-A
JA
Shin
E-S
ES
Choi
N-P
NP
Cho
H M
HM
Kim
D-H
DH
Leem
S-D
SD
Cho
D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D009062:Mouth Neoplasms / Q000378:metabolism*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D017879:Isothiocyanates; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C058305:phenethyl isothiocyanate; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053181:Caspase 8