ArticleJournal of molecular medicine (Berlin, Germany)2018
Autophagy blockade sensitizes human head and neck squamous cell carcinoma towards CYT997 through enhancing excessively high reactive oxygen species-induced apoptosis.
Article in Journal of molecular medicine (Berlin, Germany), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Natural products targeting the molecular pathology of salivary gland mucoepidermoid carcinoma: A systematic review of In vitro studies.Molecular biology reports · 2026Pooled it
- Redox-modulation of regulated cell death: implications for synergistic anticancer therapies.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Inhibition of autophagy increases head and neck cancer sensitivity to cetuximab and radiation therapy.Scientific reports · 2026Article
- Research Advances on Targets and Mechanisms in Cancers Complicated by Cardiovascular Diseases.OncoTargets and therapy · 2026Review
- Therapeutic Targeting of the GLS1-c-Myc Positive Feedback Loop Suppresses Glutaminolysis and Inhibits Progression of Head and Neck Cancer.Cancer research · 2024Article
- Identification and validation of microtubule depolymerizing agent, CYT997, as a potential drug candidate for hepatocellular carcinoma.Liver international : official journal of the International Association for the Study of the Liver · 2023Article
- Mediation of PKM2-dependent glycolytic and non-glycolytic pathways by ENO2 in head and neck cancer development.Journal of experimental & clinical cancer research : CR · 2023Article
- Autophagy awakens-the myriad roles of autophagy in head and neck cancer development and therapeutic response.Molecular carcinogenesis · 2022Review
- ATAD3A mediates activation of RAS-independent mitochondrial ERK1/2 signaling, favoring head and neck cancer development.Journal of experimental & clinical cancer research : CR · 2022Article
- Blockade of glutamine-dependent cell survival augments antitumor efficacy of CPI-613 in head and neck cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- Pharmacokinetic and Pharmacodynamic Assessment of Hydroxychloroquine in Breast Cancer.The Journal of pharmacology and experimental therapeutics · 2021Article
- FGF19/FGFR4 signaling axis confines and switches the role of melatonin in head and neck cancer metastasis.Journal of experimental & clinical cancer research : CR · 2021Article
- Targeting Reactive Oxygen Species Capacity of Tumor Cells with Repurposed Drug as an Anticancer Therapy.Oxidative medicine and cellular longevity · 2021Review
- Dual Inhibition of Autophagy and PI3K/AKT/MTOR Pathway as a Therapeutic Strategy in Head and Neck Squamous Cell Carcinoma.Cancers · 2020Article
- CPI-613 rewires lipid metabolism to enhance pancreatic cancer apoptosis via the AMPK-ACC signaling.Journal of experimental & clinical cancer research : CR · 2020Article
- Circumventing AKT-Associated Radioresistance in Oral Cancer by Novel Nanoparticle-Encapsulated Capivasertib.Cells · 2020Article
- Simultaneously inactivating Src and AKT by saracatinib/capivasertib co-delivery nanoparticles to improve the efficacy of anti-Src therapy in head and neck squamous cell carcinoma.Journal of hematology & oncology · 2019Article
- Histone deacetylase inhibitors suppress aggressiveness of head and neck squamous cell carcinoma via histone acetylation-independent blockade of the EGFR-Arf1 axis.Journal of experimental & clinical cancer research : CR · 2019Article
- Intracellular reduction in ATP levels contributes to CYT997-induced suppression of metastasis of head and neck squamous carcinoma.Journal of cellular and molecular medicine · 2019Article
- CYT997(Lexibulin) induces apoptosis and autophagy through the activation of mutually reinforced ER stress and ROS in osteosarcoma.Journal of experimental & clinical cancer research : CR · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The functional relationship between apoptosis and autophagy in anticancer drug treatment is extremely complex, and the molecular machinery is obscure. This study aims to investigate the efficacy of CYT997, a novel microtubule-disrupting agent, in head and neck squamous cell carcinomas (HNSCCs) and complete the autophagy-apoptosis puzzle involved in drug action. We report here that CYT997 exhibits anticancer activity by triggering oxidative stress-associated apoptosis in HNSCC cells. Interestingly, upregulation of autophagy by mTOR-dependent pathways appears to have a cytoprotective role in preventing apoptosis by inhibiting CYT997-induced excessively high levels of reactive oxygen species (ROS). Blockade of autophagy by ATG7 depletion or addition of autophagy inhibitor hydroxychloroquine (HCQ) sensitizes HNSCC cells to CYT997 as evidenced by enhanced ROS-associated apoptosis. Moreover, HCQ exhibits a good synergism with CYT997 on induction of apoptosis in HNSCC xenografts without cytotoxicity, suggesting combined treatment of CYT997 with autophagy inhibitors would increase the anticancer efficacy of CYT997. These findings unveil the importance of ROS in crosstalk between autophagy and apoptosis in CYT997 treatment, raising concerns that genetic or pharmacologic blockade of autophagy should be considered in the design of new therapeutics for HNSCC. KEY MESSAGES: • CYT997 exhibits anticancer activity by induction of ROS-associated apoptosis. • mTOR-dependent cytoprotective autophagy prevents CYT997-induced apoptosis. • Blockade of autophagy augments CYT997 efficacy by enhanced ROS-associated apoptosis. • Combination of autophagy inhibitors with CYT997 is more effective against HNSCC.
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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.