ArticleCell death & disease2017
Rho inhibition by lovastatin affects apoptosis and DSB repair of primary human lung cells in vitro and lung tissue in vivo following fractionated irradiation.
Article in Cell death & disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 30 citations in OpenAlex.
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- Research progress in the prevention and treatment of radiation-induced heart disease.Frontiers in pharmacology · 2025Review
- Statin Therapy Reduces Radiation-Induced Cardiotoxicity in Patients With Breast Cancer Receiving Adjuvant Radiotherapy.Journal of the American Heart Association · 2024Article
- Crosstalk between Oxidative Stress and Inflammation Induced by Ionizing Radiation in Healthy and Cancerous Cells.Current medicinal chemistry · 2024Review
- Statin therapy enhances survival in unresectable stage III lung squamous cell carcinoma with concurrent chemoradiotherapy.American journal of cancer research · 2024Article
- A Cross-Talk about Radioresistance in Lung Cancer-How to Improve Radiosensitivity According to Chinese Medicine and Medicaments That Commonly Occur in Pharmacies.International journal of molecular sciences · 2023Review
- Statins enhance the efficacy of HER2-targeting radioligand therapy in drug-resistant gastric cancers.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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- Radioprotective countermeasures for radiation injury (Review).Molecular medicine reports · 2023Review
- In Vivo Murine Models of Cardiotoxicity Due to Anticancer Drugs: Challenges and Opportunities for Clinical Translation.Journal of cardiovascular translational research · 2022Review
- Screen identifies fasudil as a radioprotector on human fibroblasts.Toxicology research · 2022Article
- Fluvastatin sensitizes pancreatic cancer cells toward radiation therapy and suppresses radiation- and/or TGF-β-induced tumor-associated fibrosis.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Radiobiological Studies of Microvascular Damage through In Vitro Models: A Methodological Perspective.Cancers · 2021Review
- Rac1, A Potential Target for Tumor Therapy.Frontiers in oncology · 2021Review
- Atorvastatin and blood flow regulate expression of distinctive sets of genes in mouse carotid artery endothelium.Current topics in membranes · 2021Article
- Extracellular Vesicles for the Treatment of Radiation Injuries.Frontiers in pharmacology · 2021Review
- DNA damage responses in murine Pre-B cells with genetic deficiencies in damage response genes.Cell cycle (Georgetown, Tex.) · 2020Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thoracic radiotherapy causes damage of normal lung tissue, which limits the cumulative radiation dose and, hence, confines the anticancer efficacy of radiotherapy and impacts the quality of life of tumor patients. Ras-homologous (Rho) small GTPases regulate multiple stress responses and cell death. Therefore, we investigated whether pharmacological targeting of Rho signaling by the HMG-CoA-reductase inhibitor lovastatin influences ionizing radiation (IR)-induced toxicity in primary human lung fibroblasts, lung epithelial and lung microvascular endothelial cells in vitro and subchronic mouse lung tissue damage following hypo-fractionated irradiation (4x4 Gy). The statin improved the repair of radiation-induced DNA double-strand breaks (DSBs) in all cell types and, moreover, protected lung endothelial cells from IR-induced caspase-dependent apoptosis, likely involving p53-regulated mechanisms. Under the in vivo situation, treatment with lovastatin or the Rac1-specific small molecule inhibitor EHT1864 attenuated the IR-induced increase in breathing frequency and reduced the percentage of γH2AX and 53BP1-positive cells. This indicates that inhibition of Rac1 signaling lowers IR-induced residual DNA damage by promoting DNA repair. Moreover, lovastatin and EHT1864 protected lung tissue from IR-triggered apoptosis and mitigated the IR-stimulated increase in regenerative proliferation. Our data document beneficial anti-apoptotic and genoprotective effects of pharmacological targeting of Rho signaling following hypo-fractionated irradiation of lung cells in vitro and in vivo. Rac1-targeting drugs might be particular useful for supportive care in radiation oncology and, moreover, applicable to improve the anticancer efficacy of radiotherapy by widening the therapeutic window of thoracic radiation exposure.
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