Protective role of Withaferin-A on immunoexpression of p53 and bcl-2 in 7,12-dimethylbenz(a)anthracene-induced experimental oral carcinogenesis.
Oral cancer, the fifth most frequent cancer worldwide, is a major health problem and accounts for highest morbidity and mortality in human populations. This form of cancer accounts for 40-50% of all cancers in developing countries including India. Despite recent advancement in the treatment, imaging and diagnosis of oral carcinoma, a 5-year survival and mortality rate for this cancer is still at 50%. Our aim was to study the protective effect of Withaferin-A on molecular pathogenesis of oral cancer by evaluating the immunoexpression of p53 and bcl-2 proteins. Oral squamous cell carcinoma was developed in the left buccal pouch of golden Syrian hamsters by painting with 0.5% 7,12-dimethylbenz(a)anthracene (DMBA), three times a week for 14 weeks. We observed 100% tumor formation with high tumor volume and burden in the DMBA alone painted hamsters as compared to control hamsters. We also observed markedly altered expression of p53 and bcl-2 proteins in tumor tissues of oral cancer bearing hamsters. Oral administration of Withaferin-A to DMBA-painted hamsters not only completely prevented oral squamous cell carcinoma formation but also significantly prevented the alterations of p53 and bcl-2 expressions. Our results thus suggest that Withaferin-A has significant protective role against DMBA induced molecular alterations in the buccal mucosa of golden Syrian hamsters.
Panjamurthy
Kuppusamy
K
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, 608 002, Tamil Nadu, India.
Manoharan
Shanmugam
S
Nirmal
Madhavan Ramados
MR
Vellaichamy
Lakshmanan
L
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D006224:Cricetinae; D004195:Disease Models, Animal; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D008297:Male; D008647:Mesocricetus; D015394:Molecular Structure; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054358:Withanolides
D002273:Carcinogens; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D054358:Withanolides; D015127:9,10-Dimethyl-1,2-benzanthracene; C009684:withaferin A; D004875:Ergosterol