Cyclooxygenase-2 expression in oral precancerous and cancerous conditions and its inhibition by caffeic acid phenyl ester-enriched propolis in human oral epidermal carcinoma KB cells

Oral cancer accounts for 3-5% of all cancers worldwide. The present study was undertaken to investigate the correlation between overexpression of cyclooxygenase-2 (COX-2) and various grades of oral cancer, and to ascertain the inhibitory effect of propolis in the human oral carcinoma cell line. For ex vivo studies, 45 patients with oral submucous fibrosis (OSF; n=15), oral leukoplakia (OLP; n=18) and oral squamous cell carcinoma (OSCC; n=18) were recruited, and a biopsy was done to determine COX-2 protein expression by Western blotting and immunohistochemistry (IHC). For the in vitro study, COX-2 levels were measured in human oral epidermal carcinoma cell line by immune blotting and IHC. The results of ex vivo studies by Western blotting revealed that COX-2 protein levels were highly upregulated in OSCC tissue, followed by OLP and OSF. The levels of COX-2 expression also showed a positive correlation with the grade (severity) of each oral precancerous and cancerous condition. Immunohistochemistry analysis revealed the presence of intense COX-2 staining in the cells of OSCC tissue, equivalent to the OLP and OSF specimens. In the in vitro study of oral carcinoma KB cells, Western blotting and IHC analysis showed that caffeic acid phenyl ester (CAPE)-rich propolis and celecoxib, a standard COX-2 inhibitor, markedly downregulated COX-2 expression. These results suggest that propolis exhibits a chemopreventive potential by lowering COX-2 expression in the oral carcinoma KB cell line. Hence, propolis might be used as an adjuvant therapy for treating oral cancer with standard chemotherapy drugs.