Diallyl Sulfide-Mediated Modulation of the Fatty Acid Synthase (FASN) Leads to Cancer Cell Death in BaP-Induced Lung Carcinogenesis in Swiss Mice

PURPOSE: Diallyl sulfide (DAS), one of the organo-sulfur secondary metabolites in garlic, has been shown to inhibit the proliferation of cancer cells. The present study aimed to evaluate the mechanism of DAS in the prevention of benzo[a]pyrene (BaP)-induced lung cancer in a murine model. MATERIALS AND METHODS: The mice were exposed to 50 mg/kg of BaP twice a week for 4 weeks in order to induce lung carcinoma. Pretreatment of mice with DAS (100 mg/kg) was started 2 weeks before BaP exposure and further continued for 21 weeks. The effect of DAS and BaP was evaluated by studying various parameters in the serum and tissues of the treated or untreated BaP-exposed mice. RESULTS: The histopathological findings demonstrated that DAS prevented the progression of malignant lung cancer and metastasis in the liver. A significant drop was observed in BaP-induced tumor marker enzymes (ADA, AHH, γ-GT, LDH) in the serum of the mice treated with DAS. Moreover, DAS treatment resulted in the recovery of antioxidant enzymes, SOD and CAT, in BaP-exposed mice. The induction of apoptosis and the destruction of cellular ROS were detected in cancer cells from the mice pre-treated with DAS. The immunohistochemical analysis revealed the up-regulation of fatty acid synthase (FASN) in the lungs and liver tissues of BaP-exposed mice and the treatment with DAS inhibited FASN expression. CONCLUSION: The findings of the present study indicated that DAS-induced apoptosis is strongly associated with the downregulation of FASN in tumor tissues. To the best of our knowledge, this is the first study that describes the role of FASN in BaP-induced lung carcinogenesis.