Biologia Molecular: Acesso Aberto

Diallyl Disulphide Protects against Colon Cancer in vitro, of HT-29 Cells and in Male Rabbits of Colon Cancer Model: An Analysis of Genetic and Epigenetic Variations

Abstract

Mohammed O Altonsy, Tito N Habib, El-Sabry A Hassanain, and Gehad S Mokhtar

Diet and dietary habits are currently accused of being among cancer causing agents. The present study was carried out in a trial to point at the beneficial anti-cancer properties of one the most Egyptian traditional food components (Garlic). We studied the anti-cancerous properties of Diallyl disulphide (DADS), a major organosulfur compound in garlic oil, on HT29 colon cancer cell line and in vivo of male rabbits (Oryctolagus cuniculus) as an animal model of colon cancer. DADS showed differential effect on the expression of a group of genes, as it down-regulated the expression of oncogenes (e.g., CTNNB1, CCDN1, BIRC5, MYC and AKT), while up-regulated the expression of tumour suppressor gene (TP53) and apoptosis regulator gene (BAX). DADS’ apoptotic effect was also seen via inducing the expression of cytochrome c and activation of caspase-3. Moreover, DADS induced chromatin configuration changes through increasing histone acetylation of histone-3 and -4. Examination of 1,2 dimethyl hydrazine (DMH) induced cancer in vivo model (O. cuniculus) showed histological changes characteristic for colon tumorigenesis such as, hyperplastic intraepithelial lesions, neoplastic changes and lymphocytes infiltration, which were strongly attenuated in animals coinjected with both DADS and DMH and were not observed in the animals that received DADS prior to DMH treatment. This study suggested the protective properties of DADS against colon cancer in vitro and in vivo.