ArticleRedox biology2020
Superoxide induced inhibition of death receptor signaling is mediated via induced expression of apoptosis inhibitory protein cFLIP.
Article in Redox biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Redox-modulation of regulated cell death: implications for synergistic anticancer therapies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- c-FLIP as a master regulator of immune homeostasis and disease mechanisms.Cell death & disease · 2026Review
- Integrated multi-omics reveals the Bacillus amyloliquefaciens BA40 against Clostridium perfringens infection in weaned piglets.Journal of advanced research · 2025Article
- Interplay between epigenetics, senescence and cellular redox metabolism in cancer and its therapeutic implications.Redox biology · 2024Review
- Antiproliferative Impact of Linagliptin on the Cervical Cancer Cell Line.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy.Cell communication and signaling : CCS · 2024Review
- (-)-Epigallocatechin-3-gallate induced apoptosis by dissociation of c-FLIP/Ku70 complex in gastric cancer cells.Journal of cellular and molecular medicine · 2023Article
- Multifaceted role of redox pattern in the tumor immune microenvironment regarding autophagy and apoptosis.Molecular cancer · 2023Review
- Editorial: The proceedings of mitochondria apoptosis and cancer (MAC 2021) virtual symposium.Frontiers in cell and developmental biology · 2022Article
- Interplay between Mitochondrial Metabolism and Cellular Redox State Dictates Cancer Cell Survival.Oxidative medicine and cellular longevity · 2021Review
- Peroxynitrite promotes serine-62 phosphorylation-dependent stabilization of the oncoprotein c-Myc.Redox biology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The death inhibitory proteins, cFLIP and Bcl-2, canonically act at different steps to regulate receptor-mediated apoptosis in cancer cells. Here we report that pharmacological or genetic means to effect an increase in intracellular superoxide result in cFLIP upregulation. Interestingly, Bcl-2 overexpression is associated with a concomitant increase in cFLIP, and reducing superoxide sensitizes Bcl-2 overexpressing cancer cells to receptor-mediated apoptosis via downregulation of cFLIP. Moreover, inhibiting glycolytic flux overcomes apoptosis resistance by superoxide-dependent downregulation of cFLIP. Superoxide-induced upregulation of cFLIP is a function of enhanced transcription, as evidenced by increases in cFLIP promoter activity and mRNA abundance. The positive effect of superoxide on cFLIP is mediated through its reaction with nitric oxide to generate peroxynitrite. Corroborating these findings in cell lines, subjecting primary cells derived from lymphoma patients to glucose deprivation ex vivo, as a means to decrease superoxide, not only reduced cFLIP expression but also significantly enhanced death receptor sensitivity. Based on this novel mechanistic insight into the redox regulation of cancer cell fate, modulation of intracellular superoxide could have potential therapeutic implications in cancers in which these two death inhibitory proteins present a therapeutic challenge.
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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.