Apoptosis induction in the hamster buccal pouch carcinogenesis model by tomato and garlic combination is mediated through modulation of Bcl-2, Bim and caspases

R Bhuvaneswari^a,b, A Sarin^c, S Nagini^a

^aDepartment of Biochemistry, Faculty of Science, Annamalai University, Tamil Nadu, India, ^bCentre for Cellular and Molecular Biology, India, ^cNational Centre for Biological Sciences, GKVK Campus, Tata Institute of Fundamental Research, Bangalore 560 065, India

Aim: The present study was designed to investigate the apoptosis-inducing effect of combined administration of tomato and garlic during 7,12-dimethyl- benz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Methods: Hamsters were divided into eight groups. Hamsters were divided into eight groups. The right buccal pouches of animals in group 1 were painted with 0.5% DMBA three times a week. Animals in groups 2 to 4 painted with DMBA as in group 1, received in addition, intragastric administration of tomato paste, aqueous garlic extract alone and in combination respectively on days alternate to DMBA application. Groups 5 through 7 were given chemopreventive agents alone. Animals in group 8 served as control. All animals were killed after an experimental period of 14 weeks. DNA fragmentation and the apoptosis-associated proteins-Bcl-2, Bim, caspases 3 and 8 in the HBP tumour and normal tissues were used as markers of apoptosis. Results: Topical application of DMBA for 14 weeks resulted in well-developed squamous cell carcinoma (SCC) associated with increased expression of Bcl-2 and decreased expression of Bim and caspases. Combined administration of tomato and garlic was found to be more effective in inhibiting the development of HBP carcinomas and inducing apoptosis than either agent used alone. This was evidenced by downregulation of Bcl-2 and upregulation of Bim and caspases 3 and 8. Conclusions: These observations suggest that tomato and garlic can act synergistically to block DMBA-induced HBP carcinomas through apoptosis induction. These results also suggest that broader spectrum of chemoprevention with less adverse effects can be attained through effective combination of functional foods.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in oral session 898 (Oncogenesis).