Dose responsive efficacy of umbelliferone on lipid peroxidation, anti-oxidant, and xenobiotic metabolism in DMBA-induced oral carcinogenesis.
This study evaluated the chemopreventive potential of umbelliferone (UMB) on 7,12- dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinogenesis. The mechanistic pathway for chemopreventive potential of UMB was evaluated by measuring the status of tumour incidence, tumour volume, and tumour burden as well as by analyzing the status of phase I, phase II detoxification agents, lipid peroxidation, antioxidants, histopathological changes and also expression patterns of cell proliferation (PCNA, Cyclin D1) and apoptotic (p53) markers using immunohistochemistry in DMBA induced hamster buccal pouch carcinogenesis. Oral squamous cell carcinoma was created by painting of 0.5% DMBA in liquid paraffin three times a week for 14 weeks, in the golden Syrian hamsters buccal pouches. We observed 100% tumor formation with high tumor volume, tumor burden and over expression of mutant p53, PCNA, and cyclin D1 in the DMBA alone painted hamsters as compared to control hamsters. Oral administration of UMB at a dose of 30mg/kg body weight to DMBA-treated hamsters completely prevented tumor incidences and restored the status of the biochemical markers in the plasma, liver and buccal mucosa, and also prevented the deregulation in the expression of molecular markers in group 4. Therefore, the present study suggests that UMB has potent chemopreventive, anti-lipid peroxidative and antioxidant potential as well as modulating effect on phase I and phase II detoxification system with reduced cell proliferation and induced apoptosis in experimental oral carcinogenesis.
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Tamil Nadu, India.
Annamalai
A
Vijayalakshmi
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Tamil Nadu, India. Electronic address: ganapathysindhu@gmail.com.
Ganapathy
G
Sindhu
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D063646:Carcinogenesis / Q000187:drug effects / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000473:pathology; D006224:Cricetinae; D019938:Cyclin D1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009061:Mouth Mucosa / Q000187:drug effects / Q000473:pathology; D009062:Mouth Neoplasms / Q000097:blood / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014468:Umbelliferones / Q000737:chemistry / Q000494:pharmacology*; D015262:Xenobiotics / Q000378:metabolism*
D000975:Antioxidants; D018809:Proliferating Cell Nuclear Antigen; D017392:Thiobarbituric Acid Reactive Substances; D016159:Tumor Suppressor Protein p53; D014468:Umbelliferones; D015262:Xenobiotics; D019938:Cyclin D1; D015127:9,10-Dimethyl-1,2-benzanthracene
Anti-oxidants; Cyclin D1; DMBA; Detoxification; Hamster buccal pouch carcinogenesis; PCNA; Umbelliferone