Diallyl Disulfide Reduces Ethyl Carbamate-Induced Cytotoxicity and Apoptosis in Intestinal and Hepatic Cells.

Abstract

Epidemiological studies indicate that lifestyle and dietary habits are associated with an increasing cancer incidence. Consuming fermented foods and alcoholic beverages and smoking can expose humans to ethyl carbamate (EC), a probable human carcinogen classified as group 2A by the International Agency for Research on Cancer (IARC). Increasing the intake of bioactive compounds can reduce EC-induced toxicity. Diallyl disulfide (DADS), found in garlic, may protect against damage induced by chemical agents and natural compounds. Here, the potential protective effect of DADS against EC was investigated by evaluating EC-induced cytotoxicity, DNA damage, apoptosis, and reactive oxygen species production in colorectal adenocarcinoma (Caco-2) and hepatocarcinoma (HepG2) cells. To this end, resazurin, comet, and annexin V-FITC staining assays and CM-H₂DCFDA markers were used to evaluate the effect on Caco-2 and HepG2 cells of protocols combining DADS (10-120 μM) and EC (80 mM). The protocols were as follows: (i) cells pretreated with DADS for 2 h and exposed to EC for 24 h; (ii) cells pretreated with DADS for 24 h and exposed to EC for 24 h; (iii) cells simultaneously exposed to DADS and EC for 24 h; (iv) cells exposed to EC for 24 h and treated with DADS for 2 h. EC induced cytotoxicity and apoptosis in Caco-2 and HepG2 cells and oxidative damage in Caco-2 cells. Combined exposure to DADS and EC for 24 h decreased EC-mediated cytotoxicity and apoptosis in both Caco-2 and HepG2 cells. These findings encourage further studies on the mechanisms of action of the combined DADS and EC.