rosmarinic-acid and Carcinoma--Squamous-Cell

Aim of the present study was to evaluate the anti-tumor effect of orally administered rosmarinic acid in 7,12-dimethylbenz(a)anthracene (DMBA) induced skin carcinogenesis in Swiss albino mice. Phase I and II detoxication agents, lipid peroxidation byproducts, antioxidants and apoptotic biomarkers were used to assess chemopreventive efficacy of rosmarinic acid in DMBA induced skin carcinogenesis. Skin squamous cell carcinoma was induced at the shaved back of mice by applying DMBA (20 microg in 0.1 mL acetone) twice weekly for 8 weeks. Tumor formation (100%) was observed within 15 weeks of treatment in DMBA alone. Marked alterations in the status of above mentioned biomarkers were observed in tumor bearing mice. Oral administration of rosmarinic acid completely prevented the formation of skin tumors during DMBA-induced mouse skin carcinogenesis. Also, oral administration of rosmarinic acid brought back the status of phase I and phase II detoxication agents, lipid peroxidation byproducts, antioxidants and apoptotic markers (p53, Bcl-2, caspase-3 and caspase-9) in DMBA treated mice. Results of the present study suggested that rosmarinic acid had potent anticancer, anti-lipid peroxidative and apoptotic effect in DMBA-induced skin carcinogenesis.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Administration, Oral; Animals; Antineoplastic Agents; Antioxidants; Carcinogens; Carcinoma, Squamous Cell; Caspase 3; Caspase 9; Cinnamates; Depsides; Drug Screening Assays, Antitumor; Humans; Mice; Proto-Oncogene Proteins c-bcl-2; Rosmarinic Acid; Skin Neoplasms; Thiobarbituric Acid Reactive Substances; Tumor Suppressor Protein p53

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.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antineoplastic Agents; Carcinogens; Carcinoma, Squamous Cell; Cinnamates; Cricetinae; Cytochrome P-450 Enzyme System; Cytochromes b5; Depsides; Disease Models, Animal; Glutathione; Glutathione Peroxidase; Lipid Peroxidation; Male; Mesocricetus; Mouth Mucosa; Mouth Neoplasms; Proto-Oncogene Proteins c-bcl-2; Rosmarinic Acid; Thiobarbituric Acid Reactive Substances; Tumor Suppressor Protein p53