3-芳基-α,β-不饱和酮介导的细胞凋亡机理研究

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...

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

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.