Coumarin modulates apoptotic, cell proliferative, inflammatory and angiogenic markers in favor of tumor inhibition during 7,12-dimethylbenz[a]anthracene- induced hamster buccal pouch carcinogenesis

Abstract

Oral carcinoma, the fifth most frequent aggressive epithelial tumor, accounts for 40-50% of all cancers in developing countries, especially in India. The aim of the present study was to assess the modulating effect of coumarin on the immunohistochemical expression pattern of apoptotic, inflammatory, angiogenic and cell proliferative markers during DMBA-induced oral carcinogenesis. Oral squamous cell carcinoma was developed in the buccal pouches of hamsters using topical application of 0.5% 7,12-dimethylbenz[a]anthracene (DMBA) three times a week for 14 weeks. The expression patterns of molecular markers were studied using immunohistochemistry (p53, Bcl-2, Bax, VEGF and PCNA), RT-PCR (cyclin D1 and NF-κB) and ELISA reader (COX-2 and c-Fos). Deregulation in the expression pattern of apoptotic (p53, Bcl-2 and Bax), cell-proliferatives (c-Fos, PCNA and cyclin D1), inflammatory (COX-2 and NF-κB) and angiogenic (VEGF) markers were noticed in the buccal mucosa of hamsters treated with DMBA alone. Oral administration of coumarin at a dose of 100 mg/kg bw protected the deregulation of above mentioned markers in hamsters treated with DMBA. The present study thus concludes that the apoptotic, anti-cell proliferatives, anti-inflammatory and anti-angiogenic potential of coumarin might have played a possible role in the prevention of oral tumors during DMBA-induced hamster buccal pouch carcinogenesis.