ArticleProceedings of the National Academy of Sciences of the United States of America2007
An NQO1- and PARP-1-mediated cell death pathway induced in non-small-cell lung cancer cells by beta-lapachone.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 1 of them a synthesis that pooled it.
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Who cites it
161 citing papers in PubMed, 1 synthesis or guideline pooled it, 347 citations in OpenAlex.
- Top 100 most-cited articles on apoptosis of non-small cell lung cancer over the past two decades: a bibliometrics analysis.Frontiers in immunology · 2024Pooled it
- Corynoxine Inhibits Tumor Growth via Targeting NQO1 and Modulating the PTPA-NQO1/PP2A Switch to Activate PP2A.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting the NAD+ Salvage Pathway Blocks Metabolic Recovery and Enhances β-Lapachone Toxicity in NQO1-Expressing Glioblastoma Cells.Cancer research communications · 2026Article
- Cytotoxic and genotoxic effects of oxime β-lapachone in human cancer cells: selectivity toward NCI-H460 and insights from molecular docking.Human cell · 2026Article
- Article
- Identification of β-Lapachone as a Potent USP22 Inhibitor That Suppresses Cancer Stemness and Enhances Chemosensitivity in Lung Adenocarcinoma.International journal of molecular sciences · 2026Article
- Alkylating agents activate an SLFN11-dependent vulnerability that confers PARP-1 inhibitor sensitivity in kidney cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Chemopreventive potential of quinones: Molecular targets and therapeutic potential.Molecular biology reports · 2026Review
- Targeting the ARL4C/RAP1/PI3K-Akt-mTOR signaling loop promotes ARL4C ubiquitination and reverses oxaliplatin resistance in colorectal cancer.Theranostics · 2026Article
- Open-Sourced In Silico Drug Screening.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Controlled Self-Immolative Release of β-Lapachone via an OptimizedJournal of the American Chemical Society · 2025Article
- Chlorogenic Acid Enhances Beta-Lapachone-Induced Cell Death by Suppressing Autophagy in NQO1-Positive Cancer Cells.Cell biology international · 2025Article
- Switching on Supramolecular DNA Junction Binding Using a Human Enzyme.Angewandte Chemie (International ed. in English) · 2025Article
- Unraveling systemic responses to NQO1-activated IB-DNQ and Rucaparib single and dual agent therapy in triple-negative breast cancers.bioRxiv : the preprint server for biology · 2025Article
- SP600125, a selective JNK inhibitor, is a potent inhibitor of NAD(P)H: quinone oxidoreductase 1 (NQO1).Acta pharmacologica Sinica · 2025Article
- Monitoring Molecular Interactions with Cell Membranes Using Time-Dependent Second Harmonic Generation Microscopy.Biochemistry · 2025Article
- A small molecule cryptotanshinone induces non-enzymatic NQO1-dependent necrosis in cancer cells through the JNK1/2/Iron/PARP/calcium pathway.Acta pharmaceutica Sinica. B · 2025Article
- Rational design of a NIR fluorescent probe for highly selective sensing of NAD(P)H quinone oxidoreductase 1 in living systems.Frontiers in chemistry · 2025Article
- UBA2 SUMOylates NQO1 and promotes the proliferation of hepatocellular carcinoma by modulating the MAPK pathway.Cancer science · 2024Article
- Natural products for enhancing the sensitivity or decreasing the adverse effects of anticancer drugs through regulating the redox balance.Chinese medicine · 2024Review
101 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Lung cancer is the number one cause of cancer-related deaths in the world. Patients treated with current chemotherapies for non-small-cell lung cancers (NSCLCs) have a survival rate of approximately 15% after 5 years. Novel approaches are needed to treat this disease. We show elevated NAD(P)H:quinone oxidoreductase-1 (NQO1) levels in tumors from NSCLC patients. beta-Lapachone, an effective chemotherapeutic and radiosensitizing agent, selectively killed NSCLC cells that expressed high levels of NQO1. Isogenic H596 NSCLC cells that lacked or expressed NQO1 along with A549 NSCLC cells treated with or without dicoumarol, were used to elucidate the mechanism of action and optimal therapeutic window of beta-lapachone. NSCLC cells were killed in an NQO1-dependent manner by beta-lapachone (LD50, approximately 4 microM) with a minimum 2-h exposure. Kinetically, beta-lapachone-induced cell death was characterized by the following: (i) dramatic reactive oxygen species (ROS) formation, eliciting extensive DNA damage; (ii) hyperactivation of poly(ADP-ribose)polymerase-1 (PARP-1); (iii) depletion of NAD+/ATP levels; and (iv) proteolytic cleavage of p53/PARP-1, indicating mu-calpain activation and apoptosis. Beta-lapachone-induced PARP-1 hyperactivation, nucleotide depletion, and apoptosis were blocked by 3-aminobenzamide, a PARP-1 inhibitor, and 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM), a Ca2+ chelator. NQO1- cells (H596, IMR-90) or dicoumarol-exposed NQO1+ A549 cells were resistant (LD50, >40 microM) to ROS formation and all cytotoxic effects of beta-lapachone. Our data indicate that the most efficacious strategy using beta-lapachone in chemotherapy was to deliver the drug in short pulses, greatly reducing cytotoxicity to NQO1- "normal" cells. beta-Lapachone killed cells in a tumorselective manner and is indicated for use against NQO1+ NSCLC cancers.
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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.