ArticleCell death & disease2021
Lysosomotropic agents including azithromycin, chloroquine and hydroxychloroquine activate the integrated stress response.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- Reprogramming Autophagy to Strengthen Antitumour Immunity: Advances in Immunotherapeutic Strategies.Immunology · 2026Review
- Pharmacological Blockade of Hypoxia-Driven Autophagy: A Therapeutic Strategy to Limit Endothelial Activation and Thrombosis.ACS pharmacology & translational science · 2026Article
- Global cellular responses to lysosomal damage.Current biology : CB · 2026Review
- Enhancing Anti-Tumor Effects of Engineered Extracellular Vesicles via Endocytosis Route Switching and Interferon Response Suppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- De Novo Serine Synthesis Is a Metabolic Vulnerability That Can Be Exploited to Overcome Sunitinib Resistance in Advanced Renal Cell Carcinoma.Cancer research · 2025Article
- Endoplasmic reticulum stress in the salivary glands of patients with primary Sjögren's syndrome, associated Sjögren's syndrome, and non-Sjögren's sicca syndrome: a comparative analysis and the influence of chloroquine.Advances in rheumatology (London, England) · 2025Article
- Innate immune and endoplasmic reticulum unfolded protein response pathways protectJournal of biosciences · 2025Article
- Article
- Emerging dimensions of autophagy in melanoma.Autophagy · 2024Review
- Achieving Endo/Lysosomal Escape Using Smart Nanosystems for Efficient Cellular Delivery.Molecules (Basel, Switzerland) · 2024Review
- Altered lipid homeostasis and autophagy precipitate diffuse alveolar hemorrhage in murine lupus.Autophagy reports · 2024Article
- ARL-17477 is a dual inhibitor of NOS1 and the autophagic-lysosomal system that prevents tumor growth in vitro and in vivo.Scientific reports · 2023Article
- Autophagy modulators influence the content of important signalling molecules in PS-positive extracellular vesicles.Cell communication and signaling : CCS · 2023Article
- Macrolide antibiotics activate the integrated stress response and promote tumor proliferation.Cell stress · 2023Article
- Magic bullets, magic shields, and antimicrobials in between.Pharmaceutical science advances · 2023Review
- Hydroxychloroquine Enhances Cytotoxic Properties of Extracellular Vesicles and Extracellular Vesicle-Mimetic Nanovesicles Loaded with Chemotherapeutics.Pharmaceutics · 2023Article
- Autophagy Paradox: Strategizing Treatment Modality in Melanoma.Current treatment options in oncology · 2023Review
- Lysosomes as a Target of Anticancer Therapy.International journal of molecular sciences · 2023Review
- Amphipathic barbiturates as marine product mimics with cytolytic and immunogenic effects on head and neck squamous cell carcinoma cell lines.Frontiers in pharmacology · 2023Article
- Synergistic Effects of Azithromycin and STING Agonist Promote IFN-I Production by Enhancing the Activation of STING-TBK1 Signaling.Journal of experimental pharmacology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The integrated stress response manifests with the phosphorylation of eukaryotic initiation factor 2α (eIF2α) on serine residue 51 and plays a major role in the adaptation of cells to endoplasmic reticulum stress in the initiation of autophagy and in the ignition of immune responses. Here, we report that lysosomotropic agents, including azithromycin, chloroquine, and hydroxychloroquine, can trigger eIF2α phosphorylation in vitro (in cultured human cells) and, as validated for hydroxychloroquine, in vivo (in mice). Cells bearing a non-phosphorylatable eIF2α mutant (S51A) failed to accumulate autophagic puncta in response to azithromycin, chloroquine, and hydroxychloroquine. Conversely, two inhibitors of eIF2α dephosphorylation, nelfinavir and salubrinal, enhanced the induction of such autophagic puncta. Altogether, these results point to the unexpected capacity of azithromycin, chloroquine, and hydroxychloroquine to elicit the integrated stress response.
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