Evaluation of a curcumin analog as an anti-cancer agent inducing ER stress-mediated apoptosis in non-small cell lung cancer cells.

Evaluation of a curcumin analog as an anti-cancer agent inducing ER stress-mediated apoptosis in non-small cell lung cancer cells.
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姜黄素类似物作为抗癌剂诱导非小细胞肺癌细胞内质网应激介导的细胞凋亡的评价

DOI:
10.1186/1471-2407-13-494
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发表时间:
2013-10-24
期刊:
影响因子:
3.8
通讯作者:
Wang Y
Wang Y
中科院分区:
医学2区
文献类型:
--
作者:
Liu Z;Sun Y;Ren L;Huang Y;Cai Y;Weng Q;Shen X;Li X;Liang G;Wang Y

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研究背景近年来,内质网(endoplasmic reticulum,ER)在细胞死亡过程中的重要作用日益受到重视.通过激活雌激素受体的压力,有效地提高肿瘤细胞死亡的药理干预措施,吸引了大量的关注抗癌therapy.MethodsA生物评价113姜黄素类似物对四种癌细胞系进行通过MTT法。采用真实的时间细胞分析法和流式细胞仪检测(1 E,4 E)-1,5-双(5-溴-2-乙氧基苯基)-1,4-戊二烯-3-酮(B82)诱导细胞凋亡的作用。然后利用Western blot、RT-qPCR和siRNA来确认B82诱导的细胞凋亡是否通过激活ER应激途径介导。结果B82对非小细胞肺癌(NSCLC)H460细胞具有较强的抗肿瘤活性。B82能明显诱导H460细胞凋亡,抑制H460肿瘤生长。结论姜黄素的一个新的单羰基类似物B82具有抗肿瘤作用,其机制可能与ER应激有关。B82可作为一种潜在的抗肿瘤药物用于治疗NSCLC。
BackgroundRecent advances have highlighted the importance of the endoplasmic reticulum (ER) in cell death processes. Pharmacological interventions that effectively enhance tumor cell death through activating ER stress have attracted a great deal of attention for anti-cancer therapy.MethodsA bio-evaluation on 113 curcumin analogs against four cancer cell lines was performed through MTT assay. Furthermore, real time cell assay and flow cytometer were used to evaluate the apoptotic induction of (1E,4E)-1,5-bis(5-bromo-2-ethoxyphenyl)penta-1,4-dien-3-one (B82). Western blot, RT-qPCR, and siRNA were then utilized to confirm whether B82-induced apoptosis is mediated through activating ER stress pathway. Finally, thein vivoanti-tumor effect of B82 was evaluated.ResultsB82 exhibited strong anti-tumor activity in non-small cell lung cancer (NSCLC) H460 cells. Treatment with B82 significantly induced apoptosis in H460 cellsin vitroand inhibited H460 tumor growthin vivo. Further studies demonstrated that the B82-induced apoptosis is mediated by activating ER stress bothin vitroandin vivo.ConclusionsA new monocarbonyl analog of curcumin, B82, exhibited anti-tumor effects on H460 cells via an ER stress-mediated mechanism. B82 could be further explored as a potential anticancer agent for the treatment of NSCLC.
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