Abstract
Our aim was to explore anti-cell proliferative and anti-angiogenic potential of andrographolide by analyzing the expression pattern of cell proliferative (PCNA, Cyclin D1) and angiogenic (VEGF) markers during 7, 12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. DMBA painting three times a week for 14 weeks in the buccal pouch of golden Syrian hamsters resulted in oral tumors which were histopathologically diagnosed as well differentiated squamous cell carcinoma. Immunohistochemical (PCNA, VEGF) and RT-PCR (Cyclin D1) studies revealed over expression of PCNA, VEGF and Cyclin D1 in the buccal mucosa of hamsters treated with DMBA alone. Oral administration of andrographolide at a dose of 50 mg/kg bw to hamsters treated with DMBA not only suppressed the histological abnormalities but also down regulated the expression of PCNA, VEGF and Cyclin D1. The results of the present study suggest that andrographolide suppressed tumor formation in the buccal mucosa of hamsters treated with DMBA through its anti-cell proliferative and anti-angiogenic potential.
Highlights
Oral cancer, a highly complex multistep process that occurs when squamous epithelium is affected by multiple genetic alterations, is the fifth most common cancer worldwide and 90% of these forms of cancers are squamous cell carcinoma (SCC) (Jemal et al, 2009)
The results of the present study suggest that andrographolide suppressed tumor formation in the buccal mucosa of hamsters treated with DMBA through its anti-cell proliferative and anti-angiogenic potential
Oral administration of andrographolide to hamsters treated with DMBA prevented the abnormal expression of PCNA and VEGF during DMBA induced oral carcinogenesis
Summary
A highly complex multistep process that occurs when squamous epithelium is affected by multiple genetic alterations, is the fifth most common cancer worldwide and 90% of these forms of cancers are squamous cell carcinoma (SCC) (Jemal et al, 2009). While oral carcinoma comprises around 40% of total malignancies in India, in western countries it accounts for only 3-5% of all cancers. Golden Syrian hamsters are commonly utilized as an experimental model of oral carcinogenesis due to their pocket (pouch) like anatomy in the mouth, which retains the carcinogen for a longer time (Manoharan et al, 2012; Singh et al, 2012). DMBA, a polycyclic aromatic hydrocarbon, is widely employed to induce oral carcinoma in experimental animals. DMBA induced experimental oral carcinogenesis in the hamster cheek pouch produces premalignant and malignant changes that resemble premalignancy and malignancy of human oral mucosa (Morris, 1961). DMBA induced oral tumors expressed biochemical and molecular characteristics similar to that of human oral tumors (Shklar et al, 2009)
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