ArticleOncotarget2019
Reactive oxygen/nitrogen species contribute substantially to the antileukemia effect of APO866, a NAD lowering agent.
Article in Oncotarget, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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
16 citing papers in PubMed, 22 citations in OpenAlex.
- NAD+ metabolism restriction boosts high-dose melphalan efficacy in patients with multiple myeloma.Blood advances · 2025Article
- Deregulation of New Cell Death Mechanisms in Leukemia.Cancers · 2024Review
- Drug repositioning strategy for the identification of novel telomere-damaging agents: A role for NAMPT inhibitors.Aging cell · 2023Article
- PARP-1 improves leukemia outcomes by inducing parthanatos during chemotherapy.Cell reports. Medicine · 2023Article
- Anticancer Activities of Novel Nicotinamide Phosphoribosyltransferase Inhibitors in Hematological Malignancies.Molecules (Basel, Switzerland) · 2023Article
- CD38-Induced Metabolic Dysfunction Primes Multiple Myeloma Cells for NADAntioxidants (Basel, Switzerland) · 2023Article
- Article
- Targeting NADFrontiers in immunology · 2023Review
- Molecular Mechanisms of Parthanatos and Its Role in Diverse Diseases.International journal of molecular sciences · 2022Review
- Gut microbiota severely hampers the efficacy of NAD-lowering therapy in leukemia.Cell death & disease · 2022Article
- Integrating RNA-seq and scRNA-seq to explore the biological significance of NAD + metabolism-related genes in the initial diagnosis and relapse of childhood B-cell acute lymphoblastic leukemia.Frontiers in immunology · 2022Article
- Erlotinib protests against LPS-induced parthanatos through inhibiting macrophage surface TLR4 expression.Cell death discovery · 2021Article
- Advances in NAD-Lowering Agents for Cancer Treatment.Nutrients · 2021Review
- Article
- Notoginseng Leaf Triterpenes Ameliorates OGD/R-Induced Neuronal Injury via SIRT1/2/3-Foxo3a-MnSOD/PGC-1Oxidative medicine and cellular longevity · 2020Article
- Beyond Energy Metabolism: Exploiting the Additional Roles of NAMPT for Cancer Therapy.Frontiers in oncology · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
APO866 is a small molecule drug that specifically inhibits nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme involved in nicotinamide adenine dinucleotide (NAD) biosynthesis from the natural precursor nicotinamide. Although, the antitumor activity of APO866 on various types of cancer models has been reported, information regarding mechanisms by which APO866 exerts its cytotoxic effects is not well defined. Here we show that APO866 induces a strong, time-dependent increase in highly reactive ROS, nitric oxide, cytosolic/mitochondrial superoxide anions and hydrogen peroxide. We provide evidence that APO866-mediated ROS production is modulated by PARP1 and triggers cell death through mitochondria depolarization and ATP loss. Genetic or pharmacologic inhibition of PARP1 prevented hydrogen peroxide accumulation, caspase activation, mitochondria depolarization, ATP loss and abrogates APO866-induced cell death, suggesting that the integrity of PARP1 status is required for cell death. Conversely, PARP1 activating drugs enhanced the anti-leukemia activity of APO866 Collectively, our studies show that APO866 induces ROS/RNS productions, which mediate its anti-leukemia effect. These results support testing new combinatorial strategies to enhance the antitumor activities of APO866.
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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.