ArticleJournal of experimental & clinical cancer research : CR2017
(S)-crizotinib induces apoptosis in human non-small cell lung cancer cells by activating ROS independent of MTH1.
Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Combined therapy with ALK inhibitors and a novel EGFR-targeting antibody‒drug conjugate as a strategy for ALK-rearranged non-small cell lung cancers.Oncogenesis · 2026Article
- Repurposing resveratrol for redox-mediated inhibition of MTH1 in breast cancer.Scientific reports · 2025Article
- LNS-8801 as a therapeutic agent for aggressive lymphomas: ROS-induced cytotoxicity and synergy with existing therapies.Blood advances · 2025Article
- Role of MTH1 in oxidative stress and therapeutic targeting of cancer.Redox biology · 2024Review
- Review
- Sacubitril/Valsartan Ameliorates Crizotinib-Induced Cardiotoxicity in Mice.Reviews in cardiovascular medicine · 2023Article
- Isotopic Radiolabeling of Crizotinib with Fluorine-18 for In Vivo Pet Imaging.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Identification of potential COVID-19 treatment compounds which inhibit SARS Cov2 prototypic, Delta and Omicron variant infection.Virology · 2022Article
- Exploring the Synergistic Anticancer Potential of Benzofuran-Oxadiazoles and Triazoles: Improved Ultrasound- and Microwave-Assisted Synthesis, Molecular Docking, Hemolytic, Thrombolytic and Anticancer Evaluation of Furan-Based Molecules.Molecules (Basel, Switzerland) · 2022Article
- Recent Research Progress of Chiral Small Molecular Antitumor-Targeted Drugs Approved by the FDA From 2011 to 2019.Frontiers in oncology · 2021Review
- Crizotinib and Doxorubicin Cooperatively Reduces Drug Resistance by Mitigating MDR1 to Increase Hepatocellular Carcinoma Cells Death.Frontiers in oncology · 2021Article
- Inhibitors of DNA Glycosylases as Prospective Drugs.International journal of molecular sciences · 2020Review
- Synthesis and in vitro anticancer activity of certain novel 1-(2-methyl-6-arylpyridin-3-yl)-3-phenylureas as apoptosis-inducing agents.Journal of enzyme inhibition and medicinal chemistry · 2019Article
- Activatable molecular agents for cancer theranostics.Chemical science · 2019Review
- Novel Crizotinib-GnRH Conjugates Revealed the Significance of Lysosomal Trapping in GnRH-Based Drug Delivery Systems.International journal of molecular sciences · 2019Article
- Increased MTH1-specific 8-oxodGTPase activity is a hallmark of cancer in colon, lung and pancreatic tissue.DNA repair · 2019Article
- Co-occurring KRAS mutation/LKB1 loss in non-small cell lung cancer cells results in enhanced metabolic activity susceptible to caloric restriction: an in vitro integrated multilevel approach.Journal of experimental & clinical cancer research : CR · 2018Article
- High expression of Copine 1 promotes cell growth and metastasis in human lung adenocarcinoma.International journal of oncology · 2018Article
- Anticancer effect of (S)-crizotinib on osteosarcoma cells by targeting MTH1 and activating reactive oxygen species.Anti-cancer drugs · 2018Article
- Immunotherapy "Shock" with vitiligo due to nivolumab administration as third line therapy in lung adenocarcinoma.Respiratory medicine case reports · 2017Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNon-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancers and is usually diagnosed at an advanced stage with poor prognosis. Targeted therapy has produced unprecedented outcomes in patients with NSCLC as a number of oncogenic drivers have been found. Crizotinib, a selective small-molecule inhibitor, has been widely used for the treatment of NSCLC patients with ALK gene rearrangements. A recent study has also shown that (S)-enantiomer of crizotinib exhibits anticancer activity by targeting the protein mutT homologue (MTH1). Since this discovery, contradictory studies have cast a doubt on MTH1 as a therapeutic target of (S)-crizotinib.
methodsNCI-H460, H1975, and A549 cells and immunodeficient mice were chosen as a model to study the (S)-crizotinib treatment. The changes induced by (S)-crizotinib treatment in cell viability, apoptosis as well as ROS, and endoplasmic reticulum stress pathway in the cells were analyzed by MTT assay, FACSCalibur, Western blotting, ROS imaging and electron microscopy.
resultsHere, we report that MTH1 does not affect survival of NSCLC cells. We found that (S)-crizotinib induces lethal endoplasmic reticulum stress (ER) response in cultured NSCLC cells by increasing intracellular levels of reactive oxygen species (ROS). Blockage of ROS production markedly reversed (S)-crizotinib-induced ER stress and cell apoptosis, independent of MTH1. We confirmed these findings in NSCLC xenograft studies and showed that (S)-crizotinib-induced ER stress and cell apoptosis.
conclusionsOur results reveal a novel antitumor mechanism of (S)-crizotinib in NSCLC which involves activation of ROS-dependent ER stress apoptotic pathway and is independent of MTH1 inhibition.
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