Anticancer Effects of Mitoquinone via Cell Cycle Arrest and Apoptosis in Canine Mammary Gland Tumor Cells

Treating female canine mammary gland tumors is crucial owing to their propensity for rapid progression and metastasis, significantly impacting the overall health and well-being of dogs. Mitoquinone (MitoQ), an antioxidant, has shown promise in inhibiting the migration, invasion, and clonogenicity of human breast cancer cells. Thus, we investigated MitoQ’s potential anticancer properties against canine mammary gland tumor cells, CMT-U27 and CF41.Mg. MitoQ markedly suppressed the proliferation and migration of both CMT-U27 and CF41.Mg cells and induced apoptotic cell death in a dose-dependent manner. Furthermore, treatment with MitoQ led to increased levels of pro-apoptotic proteins, including cleaved-caspase3, BAX, and phospho-p53. Cell cycle analysis revealed that MitoQ hindered cell progression in the G1 and S phases in CMT-U27 and CF41.Mg cells. These findings were supported using western blot analysis, demonstrating elevated levels of cleaved caspase-3, a hallmark of apoptosis, and decreased expression of cyclin-dependent kinase (CDK) 2 and cyclin D4, pivotal regulators of the cell cycle. In conclusion, MitoQ exhibits in vitro antitumor effects by inducing apoptosis and arresting the cell cycle in canine mammary gland tumors, suggesting its potential as a preventive or therapeutic agent against canine mammary cancer.

• Publication year

  2024

• Venue

  International Journal of Molecular Sciences

• Publication date

  2024-04-30

• Fields of study

  Medicine

• Identifiers
  DOI 10.3390/ijms25094923PMID 38732133PMCID 11084895
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Canine invasive mammary carcinomas as models of human breast cancer. Part 2: immunophenotypes and prognostic significance

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• Surgical treatment of mammary carcinomas in dogs with or without postoperative chemotherapy.

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  2016influential reference
• Mitochondrial ROS and cancer drug resistance: Implications for therapy.

  2015cited by this paper
• Simvastatin exhibits antiproliferative effects on spheres derived from canine mammary carcinoma cells.

  2015cited by this paper
• A mitochondrial switch promotes tumor metastasis.

  2014cited by this paper
• AKT Inhibitors Promote Cell Death in Cervical Cancer through Disruption of mTOR Signaling and Glucose Uptake

  2014cited by this paper
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  2014cited by this paper
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  2014cited by this paper
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  2013cited by this paper
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  2012cited by this paper
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  2012cited by this paper
• Mitochondrial pharmacology.

  2012cited by this paper
• Canine malignant mammary gland neoplasms with advanced clinical staging treated with carboplatin and cyclooxygenase inhibitors.

  2012cited by this paper
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  2011cited by this paper
• Protective efficacy of mitochondrial targeted antioxidant MitoQ against dichlorvos induced oxidative stress and cell death in rat brain.

  2011cited by this paper
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• Mitochondrial complex III ROS regulate adipocyte differentiation.

  2011cited by this paper
• The Akt-inhibitor Erufosine induces apoptotic cell death in prostate cancer cells and increases the short term effects of ionizing radiation

  2010cited by this paper
• The Antioxidant Transcription Factor Nrf2 Negatively Regulates Autophagy and Growth Arrest Induced by the Anticancer Redox Agent Mitoquinone*

  2010cited by this paper
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  2010cited by this paper
• Mitochondrial impairment contributes to cocaine-induced cardiac dysfunction: Prevention by the targeted antioxidant MitoQ.

  2010cited by this paper
• Tumour cell survival signalling by the ERK1/2 pathway

  2009cited by this paper
• Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?

  2009cited by this paper
• Principles of cancer therapy: oncogene and non-oncogene addiction.

  2009cited by this paper
• Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment

  2009cited by this paper
• Adjuvant gemcitabine after surgical removal of aggressive malignant mammary tumours in dogs.

  2008cited by this paper
• Akt inhibition promotes autophagy and sensitizes PTEN-null tumors to lysosomotropic agents

  2008cited by this paper
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  2007cited by this paper
• Interaction of the Mitochondria-targeted Antioxidant MitoQ with Phospholipid Bilayers and Ubiquinone Oxidoreductases*

  2007cited by this paper
• Cancer metastasis: building a framework.

  2006cited by this paper
• Postoperative adjuvant treatment of invasive malignant mammary gland tumors in dogs with doxorubicin and docetaxel.

  2006cited by this paper
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• Incidence of and survival after mammary tumors in a population of over 80,000 insured female dogs in Sweden from 1995 to 2002.

  2005influential reference
• Efficacy and toxicity of paclitaxel (Taxol) for the treatment of canine malignant tumors.

  2004cited by this paper
• Canine mammary gland tumors.

  2003cited by this paper
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  2003cited by this paper
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  2003cited by this paper
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  2003cited by this paper
• Canine neoplasia in the UK: estimates of incidence rates from a population of insured dogs.

  2002cited by this paper
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  2002cited by this paper
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  2001cited by this paper
• Mosaic blood vessels in tumors: frequency of cancer cells in contact with flowing blood.

  2000cited by this paper
• Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer.

  1996cited by this paper
• Inhibition of rat liver cytochrome P450 isozymes by isothiocyanates and their conjugates: a structure-activity relationship study.

  1996cited by this paper
• Chemoprevention by isothiocyanates

  1995cited by this paper
• Free radicals, antioxidants, and human disease: curiosity, cause, or consequence?

  1994cited by this paper
• Phase II evaluation of doxorubicin for treatment of various canine neoplasms.

  1989cited by this paper
• Absence of visual sampling in infantile nystagmus.

  1989cited by this paper

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  2024cites this paper
• Mitochondria dysfunction: A trigger for cardiovascular diseases in systemic lupus erythematosus.

  2024cites this paper