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学科主题: 药学
题名:
In vitro anticancer property of a novel thalidomide analogue through inhibition of NF-kappa B activation in HL-60 cells
作者: Li, Min1; Sun, Wan1; Yang, Ya-ping1; Xu, Bo1; Yi, Wen-yuan1; Ma, Yan-xia1; Li, Zhong-jun2; Cui, Jing-rong1
关键词: anticancer ; HL-60 ; thalidomide ; NF-kappa B ; apoptosis
刊名: ACTA PHARMACOLOGICA SINICA
发表日期: 2009
DOI: 10.1038/aps.2008.13
卷: 30, 期:1, 页:134-140
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
研究领域[WOS]: Chemistry ; Pharmacology & Pharmacy
关键词[WOS]: ALPHA-GLUCOSIDASE INHIBITORS ; MULTIPLE-MYELOMA CELLS ; STRUCTURAL DEVELOPMENT ; LEUKEMIA CELLS ; CANCER ; APOPTOSIS ; THERAPY ; PHTHALIMIDES ; DERIVATIVES ; SKELETON
英文摘要:

Aim: To investigate the anticancer property and possible mechanism of action of a novel sugar-substituted thalidomide derivative (STA-35) on HL-60 cells in vitro.

Methods: TNF-alpha-induced NF-kappa B activation was determined using a reporter gene assay. The MTT assay was used to measure cytotoxicity of the compound. The appearance of apoptotic Sub-G1 cells was detected by flow cytometry analysis. PARP cleavage and protein expression of NF-kappa B p65 and its inhibitor I kappa B were viewed by Western blotting.

Results: STA-35 (1-20 mu mol/L) suppressed TNF-alpha-induced NF-kappa B activation in transfected cells (HEK293/pNiFty-SEAP) in a dose-(1-20 mu mol/L) and time-dependent (0-48 h) manner. It was also shown that STA-35 exerted a dose- dependent inhibitory effect on HL-60 cell proliferation with an IC(50) value of 9.05 mu mol/L. In addition, STA-35 induced apoptosis in HL-60 cells, as indicated by the appearance of a Sub-G1 peak in the cell cycle distribution, as well as poly ADP-ribose polymerase (PARP) cleavage. Subsequently, both NF-kappa B p65 and its inhibitor I kappa B gradually accumulated in cytoplasmic extracts in a dose- and time-dependent manner, indicating the blockage of NF-kappa B translocation induced by TNF-alpha from the cytoplasm to the nucleus.

Conclusion: A novel sugar-substituted thalidomide derivative, STA-35, is potent toward HL-60 cells in vitro and induces apoptosis by the suppression of NF-kappa B activation.

语种: 英语
所属项目编号: 2004AA2Z3783 ; 30330690 ; 30672525
项目资助者: National High Technology Development Project ; National Natural Sciences Foundation of China
WOS记录号: WOS:000262606900015
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51532
Appears in Collections:北京大学药学院_化学生物学系_期刊论文

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作者单位: 1.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
2.Peking Univ, Dept Biol Chem, Sch Pharmaceut Sci, Beijing 100191, Peoples R China

Recommended Citation:
Li, Min,Sun, Wan,Yang, Ya-ping,et al. In vitro anticancer property of a novel thalidomide analogue through inhibition of NF-kappa B activation in HL-60 cells[J]. ACTA PHARMACOLOGICA SINICA,2009,30(1):134-140.
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