Sanchez Caroline Andolfato, Treviso Estefani Maria, Rocha Cecília Cristina de Souza, Antunes Lusânia Maria Greggi
Department of Clinical Analysis, Toxicology Food Science, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café, Vila Monte Alegre, Ribeirão Preto, SP 14040-903, Brazil.
Chem Res Toxicol. 2025 Apr 21;38(4):623-634. doi: 10.1021/acs.chemrestox.4c00439. Epub 2025 Mar 27.
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-HDCFDA 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.
流行病学研究表明，生活方式和饮食习惯与癌症发病率的上升有关。食用发酵食品、饮用酒精饮料和吸烟会使人类接触氨基甲酸乙酯（EC），这是一种国际癌症研究机构（IARC）列为2A类的可能的人类致癌物。增加生物活性化合物的摄入量可以降低EC诱导的毒性。大蒜中含有的二烯丙基二硫醚（DADS）可能预防化学试剂和天然化合物引起的损伤。在此，通过评估EC诱导的结肠腺癌（Caco-2）和肝癌（HepG2）细胞的细胞毒性、DNA损伤、凋亡和活性氧生成，研究了DADS对EC的潜在保护作用。为此，使用刃天青、彗星试验和膜联蛋白V-FITC染色试验以及CM-HDCFDA标记物来评估DADS（10-120μM）和EC（80 mM）联合方案对Caco-2和HepG2细胞的影响。方案如下：（i）细胞先用DADS预处理2小时，然后暴露于EC 24小时；（ii）细胞先用DADS预处理24小时，然后暴露于EC 24小时；（iii）细胞同时暴露于DADS和EC 24小时；（iv）细胞暴露于EC 24小时，然后用DADS处理2小时。EC诱导Caco-2和HepG2细胞的细胞毒性和凋亡以及Caco-2细胞的氧化损伤。DADS和EC联合暴露24小时可降低EC介导的Caco-2和HepG2细胞的细胞毒性和凋亡。这些发现鼓励进一步研究DADS和EC联合作用的机制。
