ArticleMolecular cancer therapeutics2008
Active roles for inhibitory kappaB kinases alpha and beta in nuclear factor-kappaB-mediated chemoresistance to doxorubicin.
Article in Molecular cancer therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- NF-κB signaling driven by oncogenic Ras contributes to tumorigenesis in a Drosophila carcinoma model.PLoS biology · 2025Article
- IKKα inhibition re-sensitizes acquired adriamycin-resistant triple negative breast cancer cells to chemotherapy-induced apoptosis.Scientific reports · 2023Article
- Nuclear Factor-κB Clinical Significance in Breast Cancer: An Immunohistochemical Study.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2023Article
- Can NF-κB Be Considered a Valid Drug Target in Neoplastic Diseases? Our Point of View.International journal of molecular sciences · 2020Review
- NF-κB Signaling in Ovarian Cancer.Cancers · 2019Review
- Ectopic expression of E3 ubiquitin-protein ligase 2 in glioma and enhances resistance to apoptosis through activating nuclear factor κ-light-chain-enhancer of B cells.Oncology letters · 2018Article
- Repurposing of Bromocriptine for Cancer Therapy.Frontiers in pharmacology · 2018Article
- An autocrine inflammatory forward-feedback loop after chemotherapy withdrawal facilitates the repopulation of drug-resistant breast cancer cells.Cell death & disease · 2017Article
- DNA damage-induced nuclear factor-kappa B activation and its roles in cancer progression.Journal of cancer metastasis and treatment · 2017Article
- A positive feedback loop involving EGFR/Akt/mTORC1 and IKK/NF-kB regulates head and neck squamous cell carcinoma proliferation.Oncotarget · 2016Article
- Pharmacogenomics of Scopoletin in Tumor Cells.Molecules (Basel, Switzerland) · 2016Article
- Article
- Doxorubicin induces atypical NF-κB activation through c-Abl kinase activity in breast cancer cells.Journal of cancer research and clinical oncology · 2013Article
- BMS-345541 sensitizes MCF-7 breast cancer cells to ionizing radiation by selective inhibition of homologous recombinational repair of DNA double-strand breaks.Radiation research · 2013Article
- IL1β induces mesenchymal stem cells migration and leucocyte chemotaxis through NF-κB.Stem cell reviews and reports · 2012Article
- Liposome-encapsulated curcumin suppresses neuroblastoma growth through nuclear factor-kappa B inhibition.Surgery · 2012Article
- Molecular marker identification for relapse prediction in 5-FU-based adjuvant chemotherapy in gastric and colorectal cancers.PloS one · 2012Article
- IKKβ regulates the repair of DNA double-strand breaks induced by ionizing radiation in MCF-7 breast cancer cells.PloS one · 2011Article
- Differential chemosensitization of P-glycoprotein overexpressing K562/Adr cells by withaferin A and Siamois polyphenols.Molecular cancer · 2010Article
- NF-kappaB activation mediates resistance to IFN beta in MLL-rearranged acute lymphoblastic leukemia.Leukemia · 2010Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Chemotherapy agents have been shown to induce the transcription factor nuclear factor-kappaB (NF-kappaB) and subsequent chemoresistance in fibrosarcomas and other cancers. The mechanism of NF-kappaB-mediated chemoresistance remains unclear, with a previous report suggesting that doxorubicin induces this response independent of the inhibitory kappaB kinases (IKK). Other studies have indicated that IKKbeta, but not IKKalpha, is required. Mouse embryo fibroblasts devoid of IKKalpha, IKKbeta, or both subunits (double knockout) were treated with doxorubicin. The absence of either IKKalpha or IKKbeta or both kinases resulted in impaired induction of NF-kappaB DNA-binding activity in response to doxorubicin. To provide a valid clinical correlate, HT1080 human fibrosarcoma cells were transfected with small interference RNA specific for IKKalpha or IKKbeta and then subsequently treated with doxorubicin. Knockdown of IKKalpha severely impaired the ability of doxorubicin to initiate NF-kappaB DNA-binding activity. However, a decrease in either IKKalpha or IKKbeta resulted in decreased phosphorylation of p65 in response to doxorubicin. The inhibition of doxorubicin-induced NF-kappaB activation by the knockdown of either catalytic subunit resulted in increased cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase and increased apoptosis when compared with doxorubicin alone. The results of this study validate current approaches aimed at NF-kappaB inhibition to improve clinical therapies. Moreover, we show that IKKalpha plays a critical role in NF-kappaB-mediated chemoresistance in response to doxorubicin and may serve as a potential target in combinational strategies to improve chemotherapeutic response.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.