ArticlePharmaceutical research2012
Chloroquine-mediated lysosomal dysfunction enhances the anticancer effect of nutrient deprivation.
Article in Pharmaceutical research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 77 citations in OpenAlex.
- Phase II randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases.Radiation oncology (London, England) · 2013Trial
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- Chloroquine Suppresses Colorectal Cancer Progression via Targeting CHKA and PFKM to inhibit the PI3K/AKT Pathway and the Warburg Effect.International journal of biological sciences · 2025Article
- Autophagy and cancer therapy.Cancer letters · 2024Review
- Protective effect of zinc against A2E-induced toxicity in ARPE-19 cells: Possible involvement of lysosomal acidification.Heliyon · 2024Article
- The Influence of Lysosomal Stress on Dental Pulp Stem Cell-Derived Schwann Cells.Biomolecules · 2024Article
- Pharmacology Progresses and Applications of Chloroquine in Cancer Therapy.International journal of nanomedicine · 2024Review
- The Question of Survival or Death: What Is the Role of Autophagy in Acute Myeloid Leukemia (AML)?International journal of hematology-oncology and stem cell research · 2022Review
- PKCeta Promotes Stress-Induced Autophagy and Senescence in Breast Cancer Cells, Presenting a Target for Therapy.Pharmaceutics · 2022Article
- Combination of Ascorbic Acid and Menadione Induces Cytotoxic Autophagy in Human Glioblastoma Cells.Oxidative medicine and cellular longevity · 2022Article
- Vacuolar proteases and autophagy in phytopathogenic fungi: A review.Frontiers in fungal biology · 2022Review
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- Potential Therapeutic Approaches through Modulating the Autophagy Process for Skin Barrier Dysfunction.International journal of molecular sciences · 2021Review
- Efficient Killing of Multidrug-Resistant Internalized Bacteria by AIEgens In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- At a glance: A history of autophagy and cancer.Seminars in cancer biology · 2020Review
- A review of nutrition and dietary interventions in oncology.SAGE open medicine · 2020Review
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- Cellular uptake, intracellular distribution and degradation of Her2-targeting silk nanospheres.International journal of nanomedicine · 2019Article
- Autophagy Machinery as a Promising Therapeutic Target in Endometrial Cancer.Frontiers in oncology · 2019Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo investigate the ability of chloroquine, a lysosomotropic autophagy inhibitor, to enhance the anticancer effect of nutrient deprivation.
methodsSerum-deprived U251 glioma, B16 melanoma and L929 fibrosarcoma cells were treated with chloroquine in vitro. Cell viability was measured by crystal violet and MTT assay. Oxidative stress, apoptosis/necrosis and intracellular acidification were analyzed by flow cytometry. Cell morphology was examined by light and electron microscopy. Activation of AMP-activated protein kinase (AMPK) and autophagy were monitored by immunoblotting. RNA interference was used for AMPK and LC3b knockdown. The anticancer efficiency of intraperitoneal chloroquine in calorie-restricted mice was assessed using a B16 mouse melanoma model.
resultsChloroquine rapidly killed serum-starved cancer cells in vitro. This effect was not mimicked by autophagy inhibitors or LC3b shRNA, indicating autophagy-independent mechanism. Chloroquine-induced lysosomal accumulation and oxidative stress, leading to mitochondrial depolarization, caspase activation and mixed apoptotic/necrotic cell death, were prevented by lysosomal acidification inhibitor bafilomycin. AMPK downregulation participated in chloroquine action, as AMPK activation reduced, and AMPK shRNA mimicked chloroquine toxicity. Chloroquine inhibited melanoma growth in calorie-restricted mice, causing lysosomal accumulation, mitochondrial disintegration and selective necrosis of tumor cells.
conclusionCombined treatment with chloroquine and calorie restriction might be useful in cancer therapy.
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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.