Nucleotide-binding oligomerization domain 2 (NOD2) activation induces apoptosis of human oral squamous cell carcinoma cells.
OBJECTIVE
Microbial Pattern-recognition receptors (PRRs), such as nucleotide-binding oligomerization domains (NODs), are essential for mammalian innate immune response. This study was designed to determine the effect of NOD1 and NOD2 agonist on innate immune responses and antitumor activity in oral squamous cell carcinoma (OSCC) cells.


METHODS
NODs expression was examined by RT-PCR, and IL-8 production by NODs agonist was examined by ELISA. Western blot analysis was performed to determine the MAPK activation in response to their agonist. Cell proliferation was determined by MTT assay. Flow cytometry and Western blot analysis were performed to determine the MDP-induced cell death.


RESULTS
The levels of NODs were apparently expressed in OSCC cells. NODs agonist, Tri-DAP and MDP, led to the production of IL-8 and MAPK activation. NOD2 agonist, MDP, inhibited the proliferation of YD-10B cells in a dose-dependent manner. Also, the ratio of Annexin V-positive cells and cleaved PARP was increased by MDP treatment in YD-10B cells, suggesting that MDP-induced cell death in YD-10B cells may be owing to apoptosis.


CONCLUSIONS
Our results indicate that NODs are functionally expressed in OSCC cells and can trigger innate immune responses. In addition, NOD2 agonist inhibited cell proliferation and induced apoptosis. These findings provide the potential value of MDP as novel candidates for antitumor agents of OSCC.
Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang Bone Regeneration Research Institute, Daejeon Dental Hospital, Wonkwang University, Daejeon, Korea.
Hyo-Eun
HE
Yoon
Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang Bone Regeneration Research Institute, Daejeon Dental Hospital, Wonkwang University, Daejeon, Korea.
Mee-Young
MY
Ahn
Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang Bone Regeneration Research Institute, Daejeon Dental Hospital, Wonkwang University, Daejeon, Korea.
Seong-Min
SM
Kwon
Division of Drug Screening and Evaluation, New Drug Development Center, Osong Medical Innovation Foundation, Cheongju, Korea.
Dong-Jae
DJ
Kim
Department of Oral and Maxillofacial Surgery, College of Dentistry, Wonkwang Bone Regeneration Research Institute, Daejeon Dental Hospital, Wonkwang University, Daejeon, Korea.
Jun
J
Lee
Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang Bone Regeneration Research Institute, Daejeon Dental Hospital, Wonkwang University, Daejeon, Korea.
Jung-Hoon
JH
Yoon
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003960:Diaminopimelic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000096:biosynthesis / Q000378:metabolism; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D053474:Nod1 Signaling Adaptor Protein / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics; D053473:Nod2 Signaling Adaptor Protein / Q000819:agonists* / Q000096:biosynthesis / Q000235:genetics; D009842:Oligopeptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D000077195:Squamous Cell Carcinoma of Head and Neck
D000970:Antineoplastic Agents; D016209:Interleukin-8; C555437:L-Ala-gamma-D-Glu-meso-diaminopimelic acid; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D009842:Oligopeptides; D012333:RNA, Messenger; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D003960:Diaminopimelic Acid; D020928:Mitogen-Activated Protein Kinases
MDP; NODs; apoptosis; oral squamous cell carcinoma