PU-H71 effectively induces degradation of IκB kinase β in the presence of TNF-α

This study is to determine if PU-H71, a heat shock protein inhibitor, induces killing of malignant breast cells together with treatment of tumor necrosis factor-α (TNF-α). The related molecular mechanisms were also studied. A primary mammary epithelial cell line HMEC2595 cells and the highly metasta...

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Bibliographic Details
Published in:Molecular and cellular biochemistry 2014-01, Vol.386 (1-2), p.135-142
Main Authors: Qu, Zhuling, Wang, Shiduan, Teng, Ruyang, Yi, Xuanlong
Format: Article
Language:English
Subjects:
Apoptosis
Apoptosis - drug effects
Base Sequence
Benzodioxoles - pharmacology
Biochemistry
Biomedical and Life Sciences
Cardiology
Cell Line
Cell Line, Tumor
DNA Primers
Down-Regulation
Heat shock proteins
Humans
I-kappa B Kinase - metabolism
Life Sciences
Medical Biochemistry
Oncology
Proteolysis
Purines - pharmacology
Reverse Transcriptase Polymerase Chain Reaction
Toy industry
Tumor necrosis factor
Tumor Necrosis Factor-alpha - metabolism
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Summary:This study is to determine if PU-H71, a heat shock protein inhibitor, induces killing of malignant breast cells together with treatment of tumor necrosis factor-α (TNF-α). The related molecular mechanisms were also studied. A primary mammary epithelial cell line HMEC2595 cells and the highly metastatic breast cell line MDA-MB-231, the HER2-positive BT-474 cells, and the ER-positive MCF7 cells were treated with PU-H71 in the presence or absence of TNF-α. The effects of PU-H71 and TNF-α treatments on cells viabilities and on intracellular signaling pathway proteins were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, apoptosis assays, immunoblot assays, and luciferase assays. It was found that TNF-α enhances the toxic effects of PU-H71 on tumor cells but not normal cells. PU-H71 treatments lead to degradation of IKKβ. Moreover, PU-H71 down-regulates the NF-κB transcriptional activity induced by TNF-α treatment. The experimental results indicated PU-H71 effectively induces cell killing of malignant breast cells in the presence of TNF-α, possibly through a mechanism related to degradation of IKKβ. It is suggested that combination of PU-H71 and TNF-α treatments might be an effective therapeutic strategy of breast malignancies.
ISSN:0300-8177
1573-4919
DOI:10.1007/s11010-013-1852-y