RESUMO
Oral cancer accounts for 40%-50% of all cancers in India. Tobacco and alcohol are the major etiological factors contributing to its pathogenesis. The aim of the present study was to explore the key mechanism behind the inhibitory effects of rosmarinic acid against 7,12-dimethylbenz(a)anthracene (DMBA)-induced oral carcinogenesis by evaluating the status of biochemical markers (lipid peroxidation, antioxidants, and detoxification enzymes) and immunoexpression patterns of p53 and bcl-2 proteins. Oral tumors were developed by painting the buccal pouches of golden Syrian hamsters with 0.5% DMBA in liquid paraffin 3 times a week for 14 weeks. We noticed 100% tumor formation in hamsters treated with DMBA alone, and the tumors were histopathologically confirmed as well-differentiated squamous cell carcinoma. Oral administration of rosmarinic acid (100 mg/kg body wt) to DMBA-treated hamsters completely prevented the tumor formation. In addition, rosmarinic acid significantly returned the status of biochemical and molecular markers to near normal range in DMBA-treated hamsters. The results of the present study suggest that rosmarinic acid suppresses oral carcinogenesis by stimulating the activities of detoxification enzymes, improves the status of lipid peroxidation and antioxidants, and downregulates the expression of p53 and bcl-2 during DMBA-induced oral carcinogenesis.
Assuntos
9,10-Dimetil-1,2-benzantraceno/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/prevenção & controle , Cinamatos/uso terapêutico , Depsídeos/uso terapêutico , Mucosa Bucal/patologia , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/prevenção & controle , Animais , Antineoplásicos/farmacologia , Carcinógenos , Carcinoma de Células Escamosas/patologia , Cinamatos/farmacologia , Cricetinae , Sistema Enzimático do Citocromo P-450/metabolismo , Citocromos b5/metabolismo , Depsídeos/farmacologia , Modelos Animais de Doenças , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Mesocricetus , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/metabolismo , Neoplasias Bucais/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Ácido RosmarínicoRESUMO
Aim was to investigate the chemopreventive potential of apigenin by analyzing the tumor incidence as well as monitoring lipid peroxidation, antioxidants and phase I and phase II detoxification as biomarkers during DMBA induced hamster buccal pouch carcinogenesis. Oral tumors were developed in the buccal pouches of golden Syrian hamsters using topical application of 0.5% DMBA (DMBA) three times a week for 14weeks. Tumor incidence, tumor volume and burden were measured in hamsters treated with 7,12-dimethylbenz(a)anthracene and DMBA+apigenin (2.5mg/kg body weight) treated hamsters. Oral administration of apigenin not only completely prevented the formation of oral tumors, it also brought back the status of lipid peroxidation, antioxidants and phase I and phase II detoxification agents to near normal range during DMBA induced oral carcinogenesis. The present study thus concludes that apigenin might have inhibited oral carcinogenesis by improving the status of antioxidant defense mechanism and modulated the activities of phase I and phase II detoxification cascade toward increased excretion of active metabolite of DMBA, during DMBA induced hamster buccal pouch carcinogenesis.
