ArticleCancer research2010
Prostate cancer radiosensitization through poly(ADP-Ribose) polymerase-1 hyperactivation.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 90 citations in OpenAlex.
- Chlorogenic Acid Enhances Beta-Lapachone-Induced Cell Death by Suppressing Autophagy in NQO1-Positive Cancer Cells.Cell biology international · 2025Article
- Review
- Application of a Specific and Sensitive NQO1 Turn-On Near-Infrared Fluorescence Probe for Live Cancer Cell and Xenografted Tumor Imaging in Nude Mice.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Article
- Radiosensitizing Effect of Dextran-Coated Iron Oxide Nanoparticles on Malignant Glioma Cells.International journal of molecular sciences · 2023Article
- β-lapachone regulates mammalian inositol pyrophosphate levels in an NQO1- and oxygen-dependent manner.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Pan-cancer and single-cell analysis reveal the prognostic value and immune response of NQO1.Frontiers in cell and developmental biology · 2023Article
- NQO1 regulates cell cycle progression at the G2/M phase.Theranostics · 2023Article
- Response prediction biomarkers and drug combinations of PARP inhibitors in prostate cancer.Acta pharmacologica Sinica · 2021Review
- X-ray repair cross-complementing protein 1 (XRCC1) loss promotes β-lapachone -induced apoptosis in pancreatic cancer cells.BMC cancer · 2021Article
- PCNA inhibition enhances the cytotoxicity of β-lapachone in NQO1-Positive cancer cells by augmentation of oxidative stress-induced DNA damage.Cancer letters · 2021Article
- A self-amplified nanocatalytic system for achieving "1 + 1 + 1 > 3" chemodynamic therapy on triple negative breast cancer.Journal of nanobiotechnology · 2021Article
- Utilizing feline oral squamous cell carcinoma patients to develop NQO1-targeted therapy.Neoplasia (New York, N.Y.) · 2021Article
- β-Lapachone Selectively Kills Hepatocellular Carcinoma Cells by Targeting NQO1 to Induce Extensive DNA Damage and PARP1 Hyperactivation.Frontiers in oncology · 2021Article
- Therapeutic Strategies and Biomarkers to Modulate PARP Activity for Targeted Cancer Therapy.Cancers · 2020Review
- Covalent-Assembly Based Fluorescent Probes for Detection of hNQO1 and Imaging in Living Cells.Frontiers in chemistry · 2020Article
- Attenuation of NAD[P]H:quinone oxidoreductase 1 aggravates prostate cancer and tumor cell plasticity through enhanced TGFβ signaling.Communications biology · 2020Article
- Augmentation of cellular NADAging cell · 2019Article
- Characterization of a highly specific NQO1-activated near-infrared fluorescent probe and its application for in vivo tumor imaging.Scientific reports · 2019Article
- NQO1-dependent, Tumor-selective Radiosensitization of Non-small Cell Lung Cancers.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The clinical experimental agent, β-lapachone (β-lap; Arq 501), can act as a potent radiosensitizer in vitro through an unknown mechanism. In this study, we analyzed the mechanism to determine whether β-lap may warrant clinical evaluation as a radiosensitizer. β-Lap killed prostate cancer cells by NAD(P)H:quinone oxidoreductase 1 (NQO1) metabolic bioactivation, triggering a massive induction of reactive oxygen species, irreversible DNA single-strand breaks (SSB), poly(ADP-ribose) polymerase-1 (PARP-1) hyperactivation, NAD(+)/ATP depletion, and μ-calpain-induced programmed necrosis. In combination with ionizing radiation (IR), β-lap radiosensitized NQO1(+) prostate cancer cells under conditions where nontoxic doses of either agent alone achieved threshold levels of SSBs required for hyperactivation of PARP-1. Combination therapy significantly elevated SSB level, γ-H2AX foci formation, and poly(ADP-ribosylation) of PARP-1, which were associated with ATP loss and induction of μ-calpain-induced programmed cell death. Radiosensitization by β-lap was blocked by the NQO1 inhibitor dicoumarol or the PARP-1 inhibitor DPQ. In a mouse xenograft model of prostate cancer, β-lap synergized with IR to promote antitumor efficacy. NQO1 levels were elevated in ∼60% of human prostate tumors evaluated relative to adjacent normal tissue, where β-lap might be efficacious alone or in combination with radiation. Our findings offer a rationale for the clinical utilization of β-lap (Arq 501) as a radiosensitizer in prostate cancers that overexpress NQO1, offering a potentially synergistic targeting strategy to exploit PARP-1 hyperactivation.
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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.