ArticleThe Journal of biological chemistry2016
Identification of Small Molecule Inhibitors of Human Cytochrome c Oxidase That Target Chemoresistant Glioma Cells.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- Copper-Induced Enhancement of Glioblastoma Tumorigenicity via Cytochrome C Oxidase.Antioxidants (Basel, Switzerland) · 2025Article
- Cellular Adaptation Takes Advantage of Atavistic Regression Programs during Carcinogenesis.Cancers · 2023Review
- Mitoferrin-1 Promotes Proliferation and Abrogates Protein Oxidation via the Glutathione Pathway in Glioblastoma.Antioxidants (Basel, Switzerland) · 2023Article
- FKBP4 regulates 5-fluorouracil sensitivity in colon cancer by controlling mitochondrial respiration.Life science alliance · 2022Article
- COX4-1 promotes mitochondrial supercomplex assembly and limits reactive oxide species production in radioresistant GBM.Cell stress · 2022Article
- Oxidative phosphorylation promotes vascular calcification in chronic kidney disease.Cell death & disease · 2022Article
- Complex Interplay of Heme-Copper Oxidases with Nitrite and Nitric Oxide.International journal of molecular sciences · 2022Review
- Catalase Overexpression Drives an Aggressive Phenotype in Glioblastoma.Antioxidants (Basel, Switzerland) · 2021Article
- Organic dust-induced mitochondrial dysfunction could be targeted via cGAS-STING or cytoplasmic NOX-2 inhibition using microglial cells and brain slice culture models.Cell and tissue research · 2021Article
- Inhibition of mitochondrial translation suppresses glioblastoma stem cell growth.Cell reports · 2021Article
- Glioma Stem-Like Cells and Metabolism: Potential for Novel Therapeutic Strategies.Frontiers in oncology · 2021Review
- Why All the Fuss about Oxidative Phosphorylation (OXPHOS)?Journal of medicinal chemistry · 2020Review
- Review
- Light-induced modulation of the mitochondrial respiratory chain activity: possibilities and limitations.Cellular and molecular life sciences : CMLS · 2020Article
- Survival-Associated Metabolic Genes in Human Papillomavirus-Positive Head and Neck Cancers.Cancers · 2020Article
- Article
- Redox-Mediated Mechanism of Chemoresistance in Cancer Cells.Antioxidants (Basel, Switzerland) · 2019Review
- Metabolism and epigenetics of pancreatic cancer stem cells.Seminars in cancer biology · 2019Review
- Acute increases inAmerican journal of physiology. Cell physiology · 2019Article
- Cytochrome C oxidase Inhibition and Cold Plasma-derived Oxidants Synergize in Melanoma Cell Death Induction.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The enzyme cytochrome c oxidase (CcO) or complex IV (EC 1.9.3.1) is a large transmembrane protein complex that serves as the last enzyme in the respiratory electron transport chain of eukaryotic mitochondria. CcO promotes the switch from glycolytic to oxidative phosphorylation (OXPHOS) metabolism and has been associated with increased self-renewal characteristics in gliomas. Increased CcO activity in tumors has been associated with tumor progression after chemotherapy failure, and patients with primary glioblastoma multiforme and high tumor CcO activity have worse clinical outcomes than those with low tumor CcO activity. Therefore, CcO is an attractive target for cancer therapy. We report here the characterization of a CcO inhibitor (ADDA 5) that was identified using a high throughput screening paradigm. ADDA 5 demonstrated specificity for CcO, with no inhibition of other mitochondrial complexes or other relevant enzymes, and biochemical characterization showed that this compound is a non-competitive inhibitor of cytochrome c When tested in cellular assays, ADDA 5 dose-dependently inhibited the proliferation of chemosensitive and chemoresistant glioma cells but did not display toxicity against non-cancer cells. Furthermore, treatment with ADDA 5 led to significant inhibition of tumor growth in flank xenograft mouse models. Importantly, ADDA 5 inhibited CcO activity and blocked cell proliferation and neurosphere formation in cultures of glioma stem cells, the cells implicated in tumor recurrence and resistance to therapy in patients with glioblastoma. In summary, we have identified ADDA 5 as a lead CcO inhibitor for further optimization as a novel approach for the treatment of glioblastoma and related cancers.
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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.