Oral squamous cell carcinoma is most prevalent and refractory cancers worldwide. Recently, chemoprevention could be a promising approach in developing countries. The present study investigates the mechanism of syringic acid (SA), a phenolic constituent of plant Alpiniacalcarata Roscoe, and their leaves are used as traditional Indian Ayurveda medicines, mediated chemoprevention on 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch carcinogenesis (HBPC). Lipid peroxidation and antioxidants were measured in the plasma and buccal tissues in experimental hamsters. Modulating effect of SA on the expression pattern of PCNA, Cyclin D1, and mutant p53 markers was used for immunoexpression and western blotting analysis. In the present study, 100% tumor formation with marked abnormalities in the biochemical parameters of lipid peroxidation and antioxidants through up-regulation of molecular markers like PCNA, Cyclin D1, and mutant p53 was accompanied with tumor-bearing hamsters. Oral administration of SA at the doses of 50 and 100 mg/kg body weight (bw) to DMBA-treated hamsters significantly inhibited adverse changes in the biochemical parameters of the plasma and buccal mucosal tissues and also down-regulation of molecular marker expression (PCNA, Cyclin D1, and mutant p53). The present study thus suggests that SA has potent anti-lipid peroxidative, antioxidant, anti-cell proliferative, and apoptosis-inducing properties during DMBA-induced HBPC.
We investigated the preventive potential of paeonol on 7,12-dimethylbenz(a)anthracene (DMBA) induced oral carcinogenesis. Oral tumors were developed in the buccal pouches of Syrian golden hamsters using topical application of 0.5% DMBA three times/week for 10 weeks. DMBA treated hamsters developed hyperplasia, dysplasia and well-differentiated squamous cell carcinoma. The animals also exhibited increased lipid oxidation, decreased antioxidant status and altered levels of detoxification agents. Paeonol treatment of DMBA treated hamsters for 14 weeks decreased tumor incidence, volume and burden Paeonol treatment also increased antioxidant activity and decreased lipid oxidation to near normal levels. Histomorphology and the expression patterns of mutant p53, cyclo-oxygenase (COX-2) and caspase-9 were investigated in the oral buccal mucosa. Paeonol exhibited protective effects against DMBA induced oral carcinogenesis owing to its antitumor, antioxidant, anti-inflammatory and apoptosis inducing properties.
In recent years, researchers have been focused on citrus flavanone, a naturally occurring bioactive substance of hesperetin. To investigate the molecular mechanism based chemopreventive efficacy of hesperetin on 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch (HBP) squamous cell carcinoma (SCC). The oral tumour was provoked by painted with 0.5% DMBA on left buccal pouch thrice a week for 10 consecutive weeks developed well-differentiated SCC and tumour formation was 100% in DMBA alone. We evaluated the chemopreventive potential of hesperetin by assessing the lipid peroxidation (LPO) by-products, status of enzymatic, non-enzymatic antioxidants, detoxifying agents etc. Moreover, modulating expression of apoptotic and cell proliferation markers were observed in HBP SCC experimental hamsters. Oral administration of hesperetin (20 mg/kg b.w.) to DMBA painted hamsters significantly reversed the stages of oral SCC. Our findings indicate that hesperetin possesses a chemopreventive effect in DMBA-induced oral SCC by exerting anti-carcinogenic property.
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