ArticleAutophagy2014
A novel cytostatic form of autophagy in sensitization of non-small cell lung cancer cells to radiation by vitamin D and the vitamin D analog, EB 1089.
Article in Autophagy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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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
60 citing papers in PubMed, 94 citations in OpenAlex.
- Research Advances of the Autophagy-Regulated Radiosensitivity.Cell proliferation · 2025Review
- Immunomodulatory role of vitamin D and emerging immunotherapies in hepatocellular carcinoma.Frontiers in nutrition · 2025Review
- Promising roles of vitamin D receptor and APRO family proteins for the development of cancer stem cells targeted malignant tumor therapy.Oncology research · 2025Review
- Evidence for cytoprotective autophagy in response to HER2-targeted monoclonal antibodies.The Journal of pharmacology and experimental therapeutics · 2025Review
- Blocking ACSL6 Compromises Autophagy via FLI1-Mediated Downregulation of COLs to Radiosensitize Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- SCFAutophagy · 2024Article
- Is Autophagy Targeting a Valid Adjuvant Strategy in Conjunction with Tyrosine Kinase Inhibitors?Cancers · 2024Review
- Advances in the molecular regulation mechanism of tumor dormancy and its therapeutic strategy.Discover oncology · 2024Review
- A Conversation with ChatGPT on Contentious Issues in Senescence and Cancer Research.Molecular pharmacology · 2024Article
- Natural products targeting autophagy and apoptosis in NSCLC: a novel therapeutic strategy.Frontiers in oncology · 2024Review
- The Cytoprotective Role of Autophagy in Response to BRAF-Targeted Therapies.International journal of molecular sciences · 2023Review
- Association of serum 25-hydroxyvitamin D with the incidence of 16 cancers, cancer mortality, and all-cause mortality among individuals with metabolic syndrome: a prospective cohort study.European journal of nutrition · 2023Article
- BRD4 Inhibition as a Strategy to Prolong the Response to Standard of Care in Estrogen Receptor-Positive Breast Cancer.Cancers · 2023Article
- Cytoprotective, Cytotoxic and Cytostatic Roles of Autophagy in Response to BET Inhibitors.International journal of molecular sciences · 2023Review
- Article
- Insights into the role of senescence in tumor dormancy: mechanisms and applications.Cancer metastasis reviews · 2023Review
- Effect of Autophagy Inhibitors on Radiosensitivity in DNA Repair-Proficient and -Deficient Glioma Cells.Medicina (Kaunas, Lithuania) · 2022Article
- Review
- Senolytic-Mediated Elimination of Head and Neck Tumor Cells Induced Into Senescence by Cisplatin.Molecular pharmacology · 2022Article
- Autophagy and cancer treatment: four functional forms of autophagy and their therapeutic applications.Journal of Zhejiang University. Science. B · 2022Review
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
Abstract
The standard of care for unresectable lung cancer is chemoradiation. However, therapeutic options are limited and patients are rarely cured. We have previously shown that vitamin D and vitamin D analogs such as EB 1089 can enhance the response to radiation in breast cancer through the promotion of a cytotoxic form of autophagy. In A549 and H460 non-small cell lung cancer (NSCLC) cells, 1,25-D3 (the hormonally active form of vitamin D) and EB 1089 prolonged the growth arrest induced by radiation alone and suppressed proliferative recovery, which translated to a significant reduction in clonogenic survival. In H838 or H358 NSCLC cells, which lack VDR/vitamin D receptor or functional TP53, respectively, 1,25-D3 failed to modify the extent of radiation-induced growth arrest or suppress proliferative recovery post-irradiation. Sensitization to radiation in H1299 NSCLC cells was evident only when TP53 was induced in otherwise tp53-null H1299 NSCLC cells. Sensitization was not associated with increased DNA damage, decreased DNA repair or an increase in apoptosis, necrosis, or senescence. Instead sensitization appeared to be a consequence of the conversion of the cytoprotective autophagy induced by radiation alone to a novel cytostatic form of autophagy by the combination of 1,25-D3 or EB 1089 with radiation. While both pharmacological and genetic suppression of autophagy or inhibition of AMPK phosphorylation sensitized the NSCLC cells to radiation alone, inhibition of the cytostatic autophagy induced by the combination treatment reversed sensitization. Evidence for selectivity was provided by lack of radiosensitization in normal human bronchial cells and cardiomyocytes. Taken together, these studies have identified a unique cytostatic function of autophagy that appears to be mediated by VDR, TP53, and possibly AMPK in the promotion of an enhanced response to radiation by 1,25-D3 and EB 1089 in NSCLC.
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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.