本研究以19种可食用硫醚类香料为原料，在体外考察其对人白血病细胞HL-60的细胞毒性作用，比较分析其构效关系，并初步探究其肿瘤细胞毒性机理。用19种硫醚类香料处理HL-60细胞，通过DNA片段化来考察其对HL-60细胞的诱导凋亡作用，并对其进行筛选。结果显示，二糠基二硫醚（DFDS）、双-（2-甲基-3-呋喃基）二硫醚（BMFDS）及甲基2-甲基-3-呋喃基二硫醚（MMFDS）具有很强的细胞毒性。利用CCK-8试剂盒检测，添加10 μM上述三种硫醚类香料使HL-60细胞的生存率分别下降41.77±1.18%、53.49±2.88%和23.63±0.90%。通过分析19种硫醚类香料的构效关系，明确硫原子数和呋喃基对硫醚类香料的HL-60细胞毒性起重要作用。为了探讨三种硫醚类香料的细胞毒性机理，采用抗氧化剂谷胱甘肽、N-乙酰半胱氨酸预处理细胞，进一步检测硫醚类香料对细胞生存率和DNA片段化的影响。结果表明，抗氧化剂对BMFDS及DFDS诱导的HL-60细胞毒性具有显著的保护作用，说明这两种硫醚类香料可能通过诱导活性氧产生而发挥细胞毒性作用。

Cytotoxicity induced by 19 kinds of edible sulfide flavors was investigated in human leukemia HL-60 cells in vitro. The structure-activity relationship was analyzed according to the comparative studies, and the mechanism of tumor cytotoxicity was initially studied. The apoptosis induced by sulfide flavors was determined by DNA fragmentation, and sulfide flavors with strong cytotoxicity were selected. The results showed that difurfuryl disulfide (DFDS), bis (2-methyl-3-furyl) disulfide (BMFDS) and methyl 2 - methyl -3- furyl disulfide (MMFDS) induced stronger cytotoxicity in HL-60 cells than the other flavors. In addition of 10 μM DFDS, BMFDS and MMFDS respectively, cell viabilities decreased by 41.77±1.18%, 53.49±2.88% and 23.63±0.90%, respectively, through using cell counting kit-8 (CCK-8). The number of sulfur atoms and furyl played important roles in cytotoxicity of HL-60 cells. Pretreatment of HL-60 cells with antioxidants of GSH and NAC showed that the antioxidants had significant protective effect on cytotoxicity induced by BMFDS and DFDS in HL-60 cells, which further suggested that BMFDS and DFDS might induce cytotoxicity by ROS production in HL-60 cells.

国家自然科学基金项目 (31201419)；辽宁省教育厅科学研究一般项目（L2012199）；辽宁省高校重大科技平台（教发[2011]191）