Modulating effect of hesperetin on the molecular expression pattern of apoptotic and cell proliferative markers in 7,12-dimethylbenz(a)anthracene-induced oral carcinogenesis

Oral squamous cell carcinoma (OSCC) is widespread malignant neoplasm and refractory cancers in worldwide. Here, we studied the chemopreventive potential of hesperetin on 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch carcinogenesis (HBPCs). Oral tumours were developed in the buccal pouches of male golden Syrian hamsters by topical application of 0.5% DMBA three times a week for 10 weeks. This causes sequentially hyperplasia, dysplasia and well differentiates squamous cell carcinoma (SCC) with up-regulation of molecular markers like mutant-p53, Caspase-3 and caspase-9 and cyclin-D1. Histology, immunohistochemistry (IHC), real time PCR (qRT-PCR) and western blot analysis of hesperetin treated animals shows a reversal in the above expression pattern to near normal in buccal mucosal tissue. Therefore, hesperetin exhibits the potential protective effect against DMBA-induced oral cancer through apoptotic and anti-proliferative properties. However, a long-term observation would be needed to confirm the possibility of malignant change of the resulted dysplastic lesions upon hesperetin pretreatment.