ArticleBreast cancer research : BCR2017
Glucocorticoids induce production of reactive oxygen species/reactive nitrogen species and DNA damage through an iNOS mediated pathway in breast cancer.
Article in Breast cancer research : BCR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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76 citing papers in PubMed, 147 citations in OpenAlex.
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- How post-translational modifications impact glucocorticoid receptor function in human pathologies.Cell communication and signaling : CCS · 2026Review
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- Fucoidan for Lung Cancer Therapy: A Review of Classification, Mechanisms, and Preclinical Studies.ACS omega · 2025Review
- Physiological Responses Vary with Molecular Damage Outcomes after Recovery from Constant Light.Integrative and comparative biology · 2025Article
- Biomarkers of psychological stress are associated with increased susceptibility to the development of breast and prostate cancer in BRCA1/2 mutation carriers.British journal of cancer · 2025Article
- Genetic analysis of stress hormone levels in hair of healthy nursery pigs and their relationships with backtest responses.Genetics · 2025Article
- Chronic stress: a fourth etiology in tumorigenesis?Molecular cancer · 2025Review
- Targeting Decidual CD16Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Lifetime chronic stress exposures, stress hormones, and biological aging: Results from the Midlife in the United States (MIDUS) study.Brain, behavior, and immunity · 2025Article
- Activation of the sympathetic-adrenal-medullary system increases DNA damage during the transition to captivity.Integrative organismal biology (Oxford, England) · 2025Article
- Defining the Differential Corticosteroid Response Basis from Multiple Omics Approaches.International journal of molecular sciences · 2024Review
- Synergistic Effects of Dietary Tryptophan and Dip Vaccination in the Immune Response of European Seabass Juveniles.International journal of molecular sciences · 2024Article
- Sleep and optic disc edema in spaceflight associated neuro-ocular syndrome (SANS).Eye (London, England) · 2024Article
- Emerging paradigms: unmasking the role of oxidative stress in HPV-induced carcinogenesis.Infectious agents and cancer · 2024Review
- Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production.Current issues in molecular biology · 2024Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPsychological stress increases the circulating levels of the stress hormones cortisol and norepinephrine (NE). Chronic exposure to elevated stress hormones has been linked to a reduced response to chemotherapy through induction of DNA damage. We hypothesize that stress hormone signalling may induce DNA damage through the production of reactive oxygen species (ROS)/reactive nitrogen species (RNS) and interference in DNA repair processes, promoting tumourigenesis.
methodsBreast cancer cell lines were incubated with physiological levels of cortisol and NE in the presence and absence of receptor antagonists and inducible nitric oxide synthase (iNOS) inhibitors and DNA damage measured using phosphorylated γ-H2AX. The rate of DNA repair was measured using comet assays and electrochemical sensors were used to detect ROS/RNS in the cell lysates from cells exposed to stress hormones. A syngeneic mouse model was used to assess the presence of iNOS in mammary tumours in stressed versus control animals and expression of iNOS was examined using western blotting and qRT-PCR.
resultsAcute exposure to cortisol and NE significantly increased levels of ROS/RNS and DNA damage and this effect was diminished in the presence of receptor antagonists. Cortisol induced DNA damage and the production of RNS was further attenuated in the presence of an iNOS inhibitor. An increase in the expression of iNOS in response to psychological stress was observed in vivo and in cortisol-treated cells. Inhibition of glucocorticoid receptor-associated Src kinase also produced a decrease in cortisol-induced RNS.
conclusionThese results demonstrate that glucocorticoids may interact with iNOS in a non-genomic manner to produce damaging levels of RNS, thus allowing an insight into the potential mechanisms by which psychological stress may impact breast cancer.
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