3-芳基-α,β-不饱和酮介导的细胞凋亡机理研究(英文)

Mechanism of cell death mediated by 3-aryl α,β-unsaturated ketone involving Michael adduct formation and induction of endoplasmic reticulum stress in human lung cancer A549 cells

选择了与3-芳基-α,β-不饱和酮结构关联的六个天然产物,研究了3-芳基-α,β-不饱和酮在诱导人肺癌细胞A549凋亡的作用与分子机制。结果表明,六个天然产物的细胞毒活性来源于3-芳基-α,β-不饱和酮结构,缺失该结构,活性明显降低;NAC明显抑制3-芳基-α,β-不饱和酮诱导的细胞毒活性,3-芳基-α,β-不饱和酮诱导的A549细胞凋亡涉及迈克尔加成、内质网应急和线粒体依赖的细胞凋亡分子机理。

Six natural products were applied to investigate the mechanism that the 3-aryl α,β-unsaturated ketone induced human lung cancer A549 cell apoptosis.The effects of these compounds with or without the structure of 3-aryl α,β-unsaturated ketone on human lung cancer A549 cells by the MTT assay were examined.It is found that these natural products with a fragment of 3-aryl α,β-unsaturated ketone,including curcumin（CUR）,chalcone（CC） and dehydrozingerone（DHZ）,were cytotoxic,with CUR CC DHZ,whereas the compounds without the 3-aryl α,β-unsaturated ketone including tetrahydrocurcumin（THC）,dihydrochalcone（DHCC） and zingerone（ZG） were not.In vitro,3-aryl α,β-unsaturated ketone formed Michael adducts with the thiol nucleophile N-acethlcysteine.In cultured cells,preincubation of the NAC with CUR,CC and DHZ decreased the cytotoxicity significantly except the THC,DHCC and ZG.Moreover,CUR and DHZ induced A549 cell apoptosis by activating the proteins JNK,P-JNK,CHOP,Bcl-2,Bax and cyto-c.These results suggested that 3-aryl α,β-unsaturated ketone mediated cell apoptosis involve in the mechanism of Michael adduct formation and induction of endoplasmic reticulum stress in human lung cancer A549 cells.