Celecoxib inhibits cell proliferation through the activation of ERK and p38 MAPK in head and neck squamous cell carcinoma cell lines.
It has been observed that several cyclooxygenase-2 (COX-2) inhibitory chemicals might inhibit proliferation of various cancer cells through COX-2-independent action. We also identified that celecoxib more selectively kills cell lines derived from head and neck squamous cell carcinoma (HNSCC) than its non-cancerous counterparts, irrespective of COX-2 expression. Herein, we investigated whether the regulation of mitogen-activated protein kinases activity might be one of the main mechanisms related to a conspicuous COX-2-independent tumor-killing effect of celecoxib in HNSCC cell lines. We assessed the effect of celecoxib on extracellular signal-regulated kinase (ERK), p38, and c-Jun NH2-terminal kinase activity by a transcription factor activation assay then evaluated, if these factors might be involved in the COX-2-independent tumor-killing effect of celecoxib by blocking their activity. We found that the blocking activation of ERK and/or p38 could reverse the celecoxib-induced cell growth inhibition by 50-80% in HNSCC cell lines, but it was not tested in cancer cells of other types. In conclusion, our study suggests that most COX-2-independent tumor-killing action of celecoxib is mediated by the upregulation of ERK and/or p38 activity in HNSCC cells. These results encourage investigation on the underlying mechanisms and detailed outcomes of mitogen-activated protein kinases activation by celecoxib more concisely, for using its excellent tumor-killing effect more safely in the clinical field of cancer treatment.
Park
Seok-Woo
SW
Cancer Research Institute, Seoul National University College of Medicine, Seoul National University Medical Research Center, Seoul National University Hospital, Seoul, Korea.
Kim
Hyo-Sun
HS
Hah
Jeong-Whun
JW
Jeong
Woo-Jin
WJ
Kim
Kwang-Hyun
KH
Sung
Myung-Whun
MW
D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000068579:Celecoxib