ArticleCell death & disease2015
Reduced mtDNA copy number increases the sensitivity of tumor cells to chemotherapeutic drugs.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 118 citations in OpenAlex.
- Association of Mitochondrial DNA Copy Number With Atopic Dermatitis in Children.Clinical and translational allergy · 2026Article
- Mitochondrial DNA Content Modulates Chemosensitivity and Cellular Adaptation in Glioblastoma Cells.The Eurasian journal of medicine · 2026Article
- Recovery from chronic PFAS exposure can reverse chemotherapy resistance and mitochondrial alterations in ovarian cancer cells.Toxicology letters · 2026Article
- Busulfan resistance in AML is associated with changes in mitochondrial copy number and lipid metabolism.Scientific reports · 2026Article
- Discovering, Integrating, and Reinterpreting the Molecular Logic of Life: From Classical Theories of Heredity to an Extended Functional Perspective on the Central Dogma.Life (Basel, Switzerland) · 2026Review
- PPA2 activates MTFP1-DNM1L fission signaling to govern mitochondrial proliferation and mitophagy.Autophagy · 2026Article
- Assessing mitochondrial phenotypes in a cybrid model of dry age-related macular degeneration.Molecular vision · 2026Article
- Mitochondrial DNA copy number reduction viaEpigenomics · 2026Article
- The role of mitochondrial DNA and RNA in promoting liver disease pathogenesis.Frontiers in cell and developmental biology · 2026Review
- Anthracyclines effect on mitochondrial function and biogenesis in normal blood cells of hodgkin lymphoma patients.Scientific reports · 2025Article
- CDH11 Contributes to Bladder Cancer Progression via Regulation of Mitochondrial Energy Metabolism.Cancer medicine · 2025Article
- Mitochondrial DNA Copy-Number Assessment Is a Potent Predictor for Prostate Cancer in White but Not Black Individuals.Cancer prevention research (Philadelphia, Pa.) · 2025Article
- Association of Mitochondrial DNA Copy Number Variations with Triple-Negative Breast Cancer: A Potential Biomarker Study.Diseases (Basel, Switzerland) · 2025Article
- Mitochondrial DNA copy number alterations: Key players in the complexity of glioblastoma (Review).Molecular medicine reports · 2025Review
- Multiomics analyses of human colorectal cancer reveal changes in mitochondrial metabolism associated with chemotherapy resistance.Frontiers in oncology · 2025Article
- Targeting the epigenome and tumor heterogeneity: advances in immunotherapy for chemoresistant metastatic colorectal cancer.Frontiers in immunology · 2025Review
- The Association Between Periodontal Inflamed Surface Area (PISA), Inflammatory Biomarkers, and Mitochondrial DNA Copy Number.Journal of clinical medicine · 2024Article
- Gastric Cancer Actively Remodels Mechanical Microenvironment to Promote Chemotherapy Resistance via MSCs-Mediated Mitochondrial Transfer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Regulation of metastatic potential by drug repurposing and mitochondrial targeting in colorectal cancer cells.BMC cancer · 2024Article
- Altered mitochondrial DNA copy number in cervical exfoliated cells among high‑risk HPV‑positive and HPV‑negative women.Experimental and therapeutic medicine · 2023Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many cancer drugs are toxic to cells by activating apoptotic pathways. Previous studies have shown that mitochondria have key roles in apoptosis in mammalian cells, but the role of mitochondrial DNA (mtDNA) copy number variation in the pathogenesis of tumor cell apoptosis remains largely unknown. We used the HEp-2, HNE2, and A549 tumor cell lines to explore the relationship between mtDNA copy number variation and cell apoptosis. We first induced apoptosis in three tumor cell lines and one normal adult human skin fibroblast cell line (HSF) with cisplatin (DDP) or doxorubicin (DOX) treatment and found that the mtDNA copy number significantly increased in apoptotic tumor cells, but not in HSF cells. We then downregulated the mtDNA copy number by transfection with shRNA-TFAM plasmids or treatment with ethidium bromide and found that the sensitivity of tumor cells to DDP or DOX was significantly increased. Furthermore, we observed that levels of reactive oxygen species (ROS) increased significantly in tumor cells with lower mtDNA copy numbers, and this might be related to a low level of antioxidant gene expression. Finally, we rescued the increase of ROS in tumor cells with lipoic acid or N-acetyl-L-cysteine and found that the apoptosis rate decreased. Our studies suggest that the increase of mtDNA copy number is a self-protective mechanism of tumor cells to prevent apoptosis and that reduced mtDNA copy number increases ROS levels in tumor cells, increases the tumor cells' sensitivity to chemotherapeutic drugs, and increases the rate of apoptosis. This research provides evidence that mtDNA copy number variation might be a promising new therapeutic target for the clinical treatment of tumors.
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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.