Carnosic acid: A potent chemopreventive agent against oral carcinogenesis

• Published in: Chemico-biological interactions 2010-12, Vol.188 (3), p.616-622
• Main Authors: Manoharan, Shanmugam, VasanthaSelvan, MuthamizhSelvan, Silvan, Simon, Baskaran, Nagarethinam, Kumar Singh, Arjun, Vinoth Kumar, Veerasamy
• Format: Article
• Language: English
• Subjects: 9,10-Dimethyl-1,2-benzanthracene - toxicity; Animals; Anticarcinogenic Agents - pharmacology; Antioxidants - metabolism; Carnosic acid; Chemoprevention; Cricetinae; Diterpenes, Abietane - pharmacology; DMBA; Hamsters; Lipid Peroxidation - drug effects; Male; Metabolic Detoxication, Phase I; Metabolic Detoxication, Phase II; Mouth Mucosa - drug effects; Mouth Mucosa - metabolism; Mouth Neoplasms - chemically induced; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; Mouth Neoplasms - prevention & control; Oral cancer; Plant Extracts - pharmacology; Thiobarbituric Acid Reactive Substances - metabolism; Tumor Burden - drug effects
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2010.08.009

The present study was aimed to investigate the chemopreventive potential of carnosic acid in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. The chemopreventive potential was assessed by analyzing the tumor incidence, tumor volume and burden as well as by measuring the status of lipid peroxidation, non-enzymatic and enzymatic antioxidants and phase I and phase II detoxification enzymes. Oral squamous cell carcinoma was developed in the buccal pouch of golden Syrian hamsters by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. In the present study, 100% tumor formation was observed in hamsters treated with DMBA alone. Also, the status of lipid peroxidation, antioxidants and phase I and phase II detoxification enzymes were significantly altered during DMBA-induced oral carcinogenesis. Oral administration of carnosic acid at a dose of 10 mg/kg body weight/day to DMBA-treated animals completely prevented the tumor formation in the hamsters’ buccal pouches. Also, carnosic acid exerted potent anti-lipid peroxidative function and stimulated the detoxification cascade during DMBA-induced hamster buccal pouch carcinogenesis. The results of the present study suggest that the chemopreventive potential of carnosic acid is probably due to its anti-lipid peroxidative potential and modulating effect on carcinogen detoxification enzymes during DMBA-induced oral carcinogenesis.