ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Proteasome inhibition by bortezomib increases IL-8 expression in androgen-independent prostate cancer cells: the role of IKKα.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Decoding NF-κB: nucleocytoplasmic shuttling dynamics, synthetic modulation and post-therapeutic behavior in cancer.Molecular biology reports · 2025Review
- Mechanisms underlying reversed TRAIL sensitivity in acquired bortezomib-resistant non-small cell lung cancer cells.Cancer drug resistance (Alhambra, Calif.) · 2024Article
- Article
- Serum deprivation initiates adaptation and survival to oxidative stress in prostate cancer cells.Scientific reports · 2020Article
- Targeting IκappaB kinases for cancer therapy.Seminars in cancer biology · 2019Review
- Regulation of Chemokines and Cytokines by Histone Deacetylases and an Update on Histone Decetylase Inhibitors in Human Diseases.International journal of molecular sciences · 2019Review
- Inhibitory-κB Kinase (IKK) α and Nuclear Factor-κB (NFκB)-Inducing Kinase (NIK) as Anti-Cancer Drug Targets.Cells · 2018Review
- Article
- Epithelial-mesenchymal transition in cancer: Role of the IL-8/IL-8R axis.Oncology letters · 2017Article
- Activation of AMP-activated Protein Kinase by Metformin Induces Protein Acetylation in Prostate and Ovarian Cancer Cells.The Journal of biological chemistry · 2016Article
- A Bowman-Birk inhibitor induces apoptosis in human breast adenocarcinoma through mitochondrial impairment and oxidative damage following proteasome 20S inhibition.Cell death discovery · 2016Article
- CCAAT/Enhancer binding protein β controls androgen-deprivation-induced senescence in prostate cancer cells.Oncogene · 2015Article
- Article
- IKK inhibition increases bortezomib effectiveness in ovarian cancer.Oncotarget · 2015Article
- Anticancer drug bortezomib increases interleukin-8 expression in human monocytes.Biochemical and biophysical research communications · 2015Article
- Transcriptional regulation of chemokine expression in ovarian cancer.Biomolecules · 2015Review
- Bortezomib inhibits expression of TGF-β1, IL-10, and CXCR4, resulting in decreased survival and migration of cutaneous T cell lymphoma cells.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Bcl3 regulates pro-survival and pro-inflammatory gene expression in cutaneous T-cell lymphoma.Biochimica et biophysica acta · 2014Article
- Proteasome inhibition increases recruitment of IκB kinase β (IKKβ), S536P-p65, and transcription factor EGR1 to interleukin-8 (IL-8) promoter, resulting in increased IL-8 production in ovarian cancer cells.The Journal of biological chemistry · 2014Article
- NFκB function and regulation in cutaneous T-cell lymphoma.American journal of cancer research · 2013Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Expression of the proinflammatory and proangiogenic chemokine IL-8, which is regulated at the transcriptional level by NF-κB, is constitutively increased in androgen-independent metastatic prostate cancer and correlates with poor prognosis. Inhibition of NF-κB-dependent transcription was used as an anticancer strategy for the development of the first clinically approved 26S proteasome inhibitor, bortezomib (BZ). Even though BZ has shown remarkable antitumor activity in hematological malignancies, it has been less effective in prostate cancer and other solid tumors; however, the mechanisms have not been fully understood. In this article, we report that proteasome inhibition by BZ unexpectedly increases IL-8 expression in androgen-independent prostate cancer PC3 and DU145 cells, whereas expression of other NF-κB-regulated genes is inhibited or unchanged. The BZ-increased IL-8 expression is associated with increased in vitro p65 NF-κB DNA binding activity and p65 recruitment to the endogenous IL-8 promoter. In addition, proteasome inhibition induces a nuclear accumulation of IκB kinase (IKK)α, and inhibition of IKKα enzymatic activity significantly attenuates the BZ-induced p65 recruitment to IL-8 promoter and IL-8 expression, demonstrating that the induced IL-8 expression is mediated, at least partly, by IKKα. Together, these data provide the first evidence, to our knowledge, for the gene-specific increase of IL-8 expression by proteasome inhibition in prostate cancer cells and suggest that targeting both IKKα and the proteasome may increase BZ effectiveness in treatment of androgen-independent prostate cancer.
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