ArticleAutophagy2021
Autophagy activation, lipotoxicity and lysosomal membrane permeabilization synergize to promote pimozide- and loperamide-induced glioma cell death.
Article in Autophagy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 105 citations in OpenAlex.
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- Drugging small-molecule compounds in autophagy-dependent cell death to overcome cancer therapy resistance.Apoptosis : an international journal on programmed cell death · 2026Review
- Risperidone induces osteoporosis and neuropsychiatric treatment resistance via SMPD1-lysosome-mediated ferroptosis: dual rescue by active vitamin D analog ED-71.Journal of advanced research · 2026Article
- Lipophagy in disease: signaling control, organelle communication, and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- Lipid metabolism reprogramming shapes the immune landscape in the tumor microenvironment.Cellular & molecular immunology · 2026Review
- Modest improvement of metabolic and behavioral deficits with long-term ambroxol treatment in a Pink1Acta pharmacologica Sinica · 2026Article
- Targeting Autophagy in Ovarian Cancer: The Emerging Role of Ginsenosides.Cancer medicine · 2026Review
- MOV10, a novel immunotherapy and prognostic biomarker, contributes to glioma development by regulating autophagy.Scientific reports · 2026Article
- Unlocking glioma vulnerabilities: targeting regulated cell death pathways for innovative therapies.Cell death discovery · 2026Review
- Revealing sphingolipid metabolism genes as biomarkers for the diagnosis of invasive pituitary adenomas in silico and in vivo.European journal of medical research · 2025Article
- Bone homeostasis regulation by in vivo generation of osteoclast-derived apoptotic bodies using targeted self-assembly.Nature communications · 2025Article
- Hypoxia response in glioblastoma cells: effect of trehalose on macropinocytosis, autophagy and cell survival.Biochemistry and biophysics reports · 2025Article
- Peroxynitrite regulates ER stress-mediated CaJournal of translational medicine · 2025Article
- Neuroglobin-promoted autophagy inhibits the proliferation, migration and invasion of human glioblastoma cells through the EGFR/PI3K/AKT/mTOR signaling pathway.Journal of translational medicine · 2025Article
- TREM2 Impedes Recovery After Spinal Cord Injury by Regulating Microglial Lysosomal Membrane Permeabilization-Mediated Autophagy.Cell proliferation · 2025Article
- Loperamide reverses 5‑FU resistance in colorectal cancer by activating autophagy.Oncology reports · 2025Article
- Comprehensive characterization of lysosome-dependent cell death reveals prognostic significance and immune landscape in colon adenocarcinoma.Scientific reports · 2025Article
- ESCRT III-mediated lysosomal repair improve renal tubular cell injury in cisplatin-induced AKI.Autophagy · 2025Article
- Elevated hexosylceramides in Parkinson's disease cause gene upregulations in neurons mimicking responses to pathogens.NPJ Parkinson's disease · 2025Article
13 more citing papers are in PubMed but not listed here.
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
Increasing evidence suggests that induction of lethal macroautophagy/autophagy carries potential significance for the treatment of glioblastoma (GBM). In continuation of previous work, we demonstrate that pimozide and loperamide trigger an ATG5- and ATG7 (autophagy related 5 and 7)-dependent type of cell death that is significantly reduced with cathepsin inhibitors and the lipid reactive oxygen species (ROS) scavenger α-tocopherol in MZ-54 GBM cells. Global proteomic analysis after treatment with both drugs also revealed an increase of proteins related to lipid and cholesterol metabolic processes. These changes were accompanied by a massive accumulation of cholesterol and other lipids in the lysosomal compartment, indicative of impaired lipid transport/degradation. In line with these observations, pimozide and loperamide treatment were associated with a pronounced increase of bioactive sphingolipids including ceramides, glucosylceramides and sphingoid bases measured by targeted lipidomic analysis. Furthermore, pimozide and loperamide inhibited the activity of SMPD1/ASM (sphingomyelin phosphodiesterase 1) and promoted induction of lysosomal membrane permeabilization (LMP), as well as release of CTSB (cathepsin B) into the cytosol in MZ-54 wild-type (WT) cells. Whereas LMP and cell death were significantly attenuated in
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