ArticleMolecular cancer therapeutics2009
IKKbeta-mediated nuclear factor-kappaB activation attenuates smac mimetic-induced apoptosis in cancer cells.
Article in Molecular cancer therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- X-linked inhibitor of apoptosis protein represents a promising therapeutic target for relapsed/refractory ALL.EMBO molecular medicine · 2023Article
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- IAP Antagonists Enhance Cytokine Production from Mouse and Human iNKT Cells.Cancer immunology research · 2018Article
- Article
- Retaining MKP1 expression and attenuating JNK-mediated apoptosis by RIP1 for cisplatin resistance through miR-940 inhibition.Oncotarget · 2014Article
- Receptor-interacting protein 1 increases chemoresistance by maintaining inhibitor of apoptosis protein levels and reducing reactive oxygen species through a microRNA-146a-mediated catalase pathway.The Journal of biological chemistry · 2014Article
- Identification of DR5 as a critical, NF-κB-regulated mediator of Smac-induced apoptosis.Cell death & disease · 2013Article
- Attenuation of TNFSF10/TRAIL-induced apoptosis by an autophagic survival pathway involving TRAF2- and RIPK1/RIP1-mediated MAPK8/JNK activation.Autophagy · 2012Article
- A superoxide-mediated mitogen-activated protein kinase phosphatase-1 degradation and c-Jun NH(2)-terminal kinase activation pathway for luteolin-induced lung cancer cytotoxicity.Molecular pharmacology · 2012Article
- Requirement of nuclear factor κB for Smac mimetic-mediated sensitization of pancreatic carcinoma cells for gemcitabine-induced apoptosis.Neoplasia (New York, N.Y.) · 2011Article
- Blocking NF-κB and Akt by Hsp90 inhibition sensitizes Smac mimetic compound 3-induced extrinsic apoptosis pathway and results in synergistic cancer cell death.Apoptosis : an international journal on programmed cell death · 2011Article
- Smac mimetic increases chemotherapy response and improves survival in mice with pancreatic cancer.Cancer research · 2010Article
- Acquired activation of the Akt/cyclooxygenase-2/Mcl-1 pathway renders lung cancer cells resistant to apoptosis.Molecular pharmacology · 2010Article
- The NF-kappaB activation pathways, emerging molecular targets for cancer prevention and therapy.Expert opinion on therapeutic targets · 2010Review
- Attenuating Smac mimetic compound 3-induced NF-kappaB activation by luteolin leads to synergistic cytotoxicity in cancer cells.Journal of cellular biochemistry · 2009Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Smac mimetics (SM) have been recently reported to kill cancer cells through the extrinsic apoptosis pathway mediated by autocrine tumor necrosis factor (TNF). SM also activates nuclear factor-kappaB (NF-kappaB). However, how SM induces NF-kappaB and the role of NF-kappaB in SM-induced cancer cell death has not been well elucidated. We found that effective blockage of NF-kappaB had no detectable effect on SM compound 3 (SMC3)-induced TNF secretion, suggesting that the induction of TNF by SMC3 is independent of NF-kappaB. Conversely, SMC3-induced NF-kappaB activation was found to be mediated by autocrine TNF because this effect of SMC3 was effectively inhibited when TNF was blocked with either a TNF neutralizing antibody or TNF small interfering RNA. In addition, although SMC3 dramatically reduced c-IAP1 level, it had marginal effect on c-IAP2 expression, TNF-induced RIP modification, NF-kappaB activation, and downstream antiapoptosis NF-kappaB target expression. Furthermore, blocking NF-kappaB by targeting IKKbeta or RelA substantially potentiated SMC3-induced cytotoxicity, suggesting that the NF-kappaB pathway inhibits SMC3-induced apoptosis in cancer cells. Our results show that through TNF autocrine, SM induces an IKKbeta-mediated NF-kappaB activation pathway that protects cancer cells against SM-induced apoptosis, and thus, NF-kappaB blockage could be an effective approach for improving the anticancer value of SM.
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Registered trials
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.