ArticleCancer science2008
DNA polymerase gamma inhibition by vitamin K3 induces mitochondria-mediated cytotoxicity in human cancer cells.
Article in Cancer science, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 77 citations in OpenAlex.
- Targeting mitochondria as a potential therapeutic strategy against radioresistance in cancer.Frontiers in oncology · 2026Review
- Recent Advances in Mitochondria-Targeted Nano-Drug Delivery Systems for Cancer Therapy.International journal of nanomedicine · 2026Review
- Perturbation of Copper Homeostasis Sensitizes Cancer Cells to Elevated Temperature.International journal of molecular sciences · 2023Article
- Mitochondria Deregulations in Cancer Offer Several Potential Targets of Therapeutic Interventions.International journal of molecular sciences · 2023Review
- Targeting DNA polymerase β elicits synthetic lethality with mismatch repair deficiency in acute lymphoblastic leukemia.Leukemia · 2023Article
- Redox-Cycling "Mitocans" as Effective New Developments in Anticancer Therapy.International journal of molecular sciences · 2023Article
- Targeting Energy Metabolism in Cancer Treatment.International journal of molecular sciences · 2022Review
- Targeting mitochondrial DNA polymerase gamma for selective inhibition of MLH1 deficient colon cancer growth.PloS one · 2022Article
- Large-scale and high-resolution mass spectrometry-based proteomics profiling defines molecular subtypes of esophageal cancer for therapeutic targeting.Nature communications · 2021Article
- Identification of Vitamin K3 and its analogues as covalent inhibitors of SARS-CoV-2 3CLInternational journal of biological macromolecules · 2021Article
- An understanding of mitochondria and its role in targeting nanocarriers for diagnosis and treatment of cancer.Asian journal of pharmaceutical sciences · 2021Review
- Exosome-mediated radiosensitizing effect on neighboring cancer cells via increase in intracellular levels of reactive oxygen species.Oncology reports · 2021Article
- Natural Agents Targeting Mitochondria in Cancer.International journal of molecular sciences · 2020Review
- Selective Targeting of Cancerous Mitochondria and Suppression of Tumor Growth Using Redox-Active Treatment Adjuvant.Oxidative medicine and cellular longevity · 2020Article
- Vitamin K3 derivative induces apoptotic cell death in neuroblastoma via downregulation of MYCN expression.Biochemistry and biophysics reports · 2019Article
- Off-Target Effects of Drugs that Disrupt Human Mitochondrial DNA Maintenance.Frontiers in molecular biosciences · 2017Review
- Titanium peroxide nanoparticles enhanced cytotoxic effects of X-ray irradiation against pancreatic cancer model through reactive oxygen species generation in vitro and in vivo.Radiation oncology (London, England) · 2016Article
- Reactive oxygen species stimulate mitochondrial allele segregation toward homoplasmy in human cells.Molecular biology of the cell · 2016Article
- Cytotoxic and apoptotic effects of menadione on rat hepatocellular carcinoma cells.Cytotechnology · 2015Article
- Novel therapy for locally advanced triple-negative breast cancer.International journal of oncology · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Among the vitamin K (VK) compounds, VK3 exhibits distinct cytotoxic activity in cancer cells and is thought to affect redox cycling; however, the underlying mechanisms remain unclear. Here we demonstrate that VK3 selectively inhibits DNA polymerase (pol) gamma, the key enzyme responsible for mitochondrial DNA replication and repair. VK3 at 30 microM inhibited pol gamma by more than 80%, caused impairment of mitochondrial DNA replication and repair, and induced a significant increase in reactive oxygen species (ROS), leading to apoptosis. At a lower concentration (3 microM), VK3 did not cause a significant increase in ROS, but was able to effectively inhibit cell proliferation, which could be reversed by supplementing glycolytic substrates. The cytotoxic action of VK3 was independent of p53 tumor suppressor gene status. Interestingly, VK3 only inhibited pol gamma but did not affect other pol including human pol alpha, pol beta, pol delta, and pol epsilon. VK1 and VK2 exhibited no inhibitory effect on any of the pol tested. These data together suggest that the inhibition of pol gamma by VK3 is relatively specific, and that this compound seems to exert its anticancer activity by two possible mechanisms in a concentration-dependent manner: (1) induction of ROS-mediated cell death at high concentrations; and (2) inhibition of cell proliferation at lower concentrations likely through the suppression of mitochondrial respiratory function. These findings may explain various cytotoxic actions induced by VK3, and may pave the way for the further use of VK3.
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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.