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The mechanism of apoptosis induced by a novel thioredoxin reductase inhibitor in A549 cells: Possible involvement of nuclear factor-kappa B-dependent pathway
Lan, Linxiang; Zhao, Fang; Wang, Yan; Zeng, Huihui
关键词thioredoxin system thioredoxin reductase inhibitor I kappa B NF-kappa B NF-kappa B regulated anti-apoptosis gene apoptosis
刊名EUROPEAN JOURNAL OF PHARMACOLOGY
2007-01-26
DOI10.1016/j.ejphar.2006.10.037
555期:2-3页:83-92
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pharmacology & Pharmacy
研究领域[WOS]Pharmacology & Pharmacy
关键词[WOS]MAMMALIAN THIOREDOXIN ; DIRECT ASSOCIATION ; REDOX REGULATION ; HUMAN TUMORS ; IN-VITRO ; CANCER ; FAMILY ; TARGET ; GROWTH ; DEATH
英文摘要

1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)]ethane (BBSKE, PCT: CN02/00412), a novel thioredoxin reductase inhibitor previously synthesized in our lab, has been demonstrated to inhibit the growth of a variety of human cancer cells and to induce apoptosis. Here we report on the potential molecular mechanism of apoptosis induced by BBSKE in A549 cells. The treatment of BBSKE reduced the protein levels of Bcl-2, Bcl-xL, procaspase-9 and procaspase-3, and caused the release of cytochrome C from the mitochondria to the cytosol in a dose-dependent manner, suggesting the onset of mitochondria-dependent apoptosis. Through electrophoretic mobility shift assay (EMSA), the DNA-binding activity of nuclear factor-kappa B (NF-kappa B) was found to be attenuated after BBSKE treatment, accompanied by the diminution of the immunoprecipitated complex of thioredoxin and NF-kappa B in co-immunoprecipitation experiments. Meanwhile, the ratio of pI kappa B-alpha to I kappa B-alpha and the subcellular localization of p65 between cytoplasm and nucleus were not significantly altered by BBSKE treatment, as demonstrated in western analysis and immunocytochemistry assay. Furthermore, the mRNA levels of the NF-kappa B regulated anti-apoptosis genes Bcl-2, Bcl-xL, cIAP-2 and XIAP were decreased in a dose-dependent manner after BBSKE treatment. All the above observations suggest that BBSKE induce rnitochondria-dependent apoptosis in A549 cells probably through suppressing the thioredoxin reductase-thioredoxin-NF-kappa B pathway. (c) 2006 Elsevier B.V. All rights reserved.

语种英语
WOS记录号WOS:000244124100001
Citation statistics
Cited Times:33[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62097
Collection北京大学药学院
作者单位1.Peking Univ, Hosp 1, Beijing 100034, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, Beijing 100083, Peoples R China
Recommended Citation
GB/T 7714
Lan, Linxiang,Zhao, Fang,Wang, Yan,et al. The mechanism of apoptosis induced by a novel thioredoxin reductase inhibitor in A549 cells: Possible involvement of nuclear factor-kappa B-dependent pathway[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2007,555(2-3):83-92.
APA Lan, Linxiang,Zhao, Fang,Wang, Yan,&Zeng, Huihui.(2007).The mechanism of apoptosis induced by a novel thioredoxin reductase inhibitor in A549 cells: Possible involvement of nuclear factor-kappa B-dependent pathway.EUROPEAN JOURNAL OF PHARMACOLOGY,555(2-3),83-92.
MLA Lan, Linxiang,et al."The mechanism of apoptosis induced by a novel thioredoxin reductase inhibitor in A549 cells: Possible involvement of nuclear factor-kappa B-dependent pathway".EUROPEAN JOURNAL OF PHARMACOLOGY 555.2-3(2007):83-92.
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