ArticlePloS one2012
Inhibition of mitochondria- and endoplasmic reticulum stress-mediated autophagy augments temozolomide-induced apoptosis in glioma cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 118 citations in OpenAlex.
- ARL13B is regulated by the ERK/P90 pathway and mediates TMZ resistance in glioblastoma via microvesicles.Scientific reports · 2026Article
- Morphofunctional Heterogeneity and Plasticity of Glioblastoma Cells Induced to Senescence by Temozolomide.Aging cell · 2026Article
- The evolution of chemotherapy in brain tumors: from historical milestones to precision medicine in glioblastoma.Exploration of targeted anti-tumor therapy · 2026Review
- Sanggenol L Enhances Temozolomide Drug Sensitivity by Inhibiting Mitophagy and Inducing Apoptosis Through the Regulation of the TRIM16-OPTN Axis in Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Identification of Autophagy-Related Prognostic Signature for Glioblastoma Standard Therapy.Biomolecules & therapeutics · 2025Article
- Review
- Lucanthone, a Potential PPT1 Inhibitor, Perturbs Stemness, Reduces Tumor Microtube Formation, and Slows the Growth of Temozolomide-Resistant Gliomas In Vivo.The Journal of pharmacology and experimental therapeutics · 2024Article
- 4″-Alkyl EGCG Derivatives Induce Cytoprotective Autophagy Response by Inhibiting EGFR in Glioblastoma Cells.ACS omega · 2024Article
- Mammalian target of rapamycin inhibition protects glioma cells from temozolomide-induced cell death.Cell death discovery · 2024Article
- Beclin-1: a therapeutic target at the intersection of autophagy, immunotherapy, and cancer treatment.Frontiers in immunology · 2024Review
- The Combination of ΔCancers · 2022Article
- Alterations in Molecular Profiles Affecting Glioblastoma Resistance to Radiochemotherapy: Where Does the Good Go?Cancers · 2022Review
- Role of Mitochondria in Physiology of Chondrocytes and Diseases of Osteoarthritis and Rheumatoid Arthritis.Cartilage · 2021Review
- Olaparib Is a Mitochondrial Complex I Inhibitor That Kills Temozolomide-Resistant Human Glioblastoma Cells.International journal of molecular sciences · 2021Article
- Chloroquine combined with concurrent radiotherapy and temozolomide for newly diagnosed glioblastoma: a phase IB trial.Autophagy · 2021Article
- Cinnamophilin enhances temozolomide-induced cytotoxicity against malignant glioma: the roles of ROS and cell cycle arrest.Translational cancer research · 2021Article
- Autophagy inhibition is the next step in the treatment of glioblastoma patients following the Stupp era.Cancer gene therapy · 2021Review
- Guanabenz Sensitizes Glioblastoma Cells to Sunitinib by Inhibiting GADD34-Mediated Autophagic Signaling.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Mechanisms of temozolomide resistance in glioblastoma - a comprehensive review.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy is a crucial process for cells to maintain homeostasis and survival through degradation of cellular proteins and organelles, including mitochondria and endoplasmic reticula (ER). We previously demonstrated that temozolomide (TMZ), an alkylating agent for brain tumor chemotherapy, induced reactive oxygen species (ROS)/extracellular signal-regulated kinase (ERK)-mediated autophagy to protect glioma cells from apoptosis. In this study, we investigated the role of mitochondrial damage and ER stress in TMZ-induced cytotoxicity. Mitochondrial depolarization and mitochondrial permeability transition pore (MPTP) opening were observed as a prelude to TMZ-induced autophagy, and these were followed by the loss of mitochondrial mass. Electron transport chain (ETC) inhibitors, such as rotenone (a complex I inhibitor), sodium azide (a complex IV inhibitor), and oligomycin (a complex V inhibitor), or the MPTP inhibitor, cyclosporine A, decreased mitochondrial damage-mediated autophagy, and therefore increased TMZ-induced apoptosis. TMZ treatment triggered ER stress with increased expression of GADD153 and GRP78 proteins, and deceased pro-caspase 12 protein. ER stress consequently induced autophagy through c-Jun N-terminal kinases (JNK) and Ca(2+) signaling pathways. Combination of TMZ with 4-phenylbutyrate (4-PBA), an ER stress inhibitor, augmented TMZ-induced cytotoxicity by inhibiting autophagy. Taken together, our data indicate that TMZ induced autophagy through mitochondrial damage- and ER stress-dependent mechanisms to protect glioma cells. This study provides evidence that agents targeting mitochondria or ER may be potential anticancer strategies.
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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.