ArticleMolecular cancer therapeutics2009
Nuclear factor kappaB inhibitors alleviate and the proteasome inhibitor PS-341 exacerbates radiation toxicity in zebrafish embryos.
Article in Molecular cancer therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
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- Evaluation of Epigenetic and Radiomodifying Effects during Radiotherapy Treatments in Zebrafish.International journal of molecular sciences · 2021Review
- Therapeutic Potential of RTA 404 in Human Brain Malignant Glioma Cell Lines via Cell Cycle Arrest via p21/AKT Signaling.BioMed research international · 2021Article
- Yolk sac-derived Pdcd11-positive cells modulate zebrafish microglia differentiation through the NF-κB-Tgfβ1 pathway.Cell death and differentiation · 2021Article
- Targets for protection and mitigation of radiation injury.Cellular and molecular life sciences : CMLS · 2020Review
- Deep insights into the response of human cervical carcinoma cells to a new cyano enone-bearing triterpenoid soloxolone methyl: a transcriptome analysis.Oncotarget · 2019Article
- l-Alpha Glycerylphosphorylcholine as a Potential Radioprotective Agent in Zebrafish Embryo Model.Zebrafish · 2016Article
- Cnbp ameliorates Treacher Collins Syndrome craniofacial anomalies through a pathway that involves redox-responsive genes.Cell death & disease · 2016Article
- Emerging targets for radioprotection and radiosensitization in radiotherapy.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- The triterpenoid RTA 408 is a robust mitigator of hematopoietic acute radiation syndrome in mice.Radiation research · 2015Article
- Radioprotector WR-2721 and mitigating peptidoglycan synergistically promote mouse survival through the amelioration of intestinal and bone marrow damage.Journal of radiation research · 2015Article
- Radiation protection of the gastrointestinal tract and growth inhibition of prostate cancer xenografts by a single compound.Molecular cancer therapeutics · 2014Article
- Proteasome inhibitor PS-341 attenuates flow-induced pulmonary arterial hypertension.Clinical and experimental medicine · 2014Article
- CDDO-Me protects normal lung and breast epithelial cells but not cancer cells from radiation.PloS one · 2014Article
- Emergence of zebrafish models in oncology for validating novel anticancer drug targets and nanomaterials.Drug discovery today · 2013Review
- Imaging vertebrate digestive function and lipid metabolismDrug discovery today. Disease models · 2013Article
- Synthetic oleanane triterpenoids: multifunctional drugs with a broad range of applications for prevention and treatment of chronic disease.Pharmacological reviews · 2012Review
- Radiation damage and radioprotectants: new concepts in the era of molecular medicine.The British journal of radiology · 2012Article
- Injury-dependent Müller glia and ganglion cell reprogramming during tissue regeneration requires Apobec2a and Apobec2b.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Inflammatory changes are a major component of the normal tissue response to ionizing radiation, and increased nuclear factor kappaB (NF-kappaB) activity is an important mediator of inflammatory responses. Here, we used zebrafish embryos to assess the capacity of two different classes of pharmacologic agents known to target NF-kappaB to modify radiation toxicity in the vertebrate organism. These were proteasome inhibitors, including lactacystin, MG132, and PS-341 (Bortezomib/VELCADE), and direct inhibitors of NF-kappaB activity, including ethyl pyruvate (EP) and the synthetic triterpenoid CDDO-TFEA (RTA401), among others. The proteasome inhibitors either did not significantly affect radiation sensitivity of zebrafish embryos (MG132, lactacystin) or rendered zebrafish embryos more sensitive to the lethal effects of ionizing radiation (PS-341). Radiosensitization by PS-341 was reduced in fish with impaired p53 expression or function but not associated with enhanced expression of select p53 target genes. In contrast, the direct NF-kappaB inhibitors EP and CDDO-TFEA significantly improved overall survival of lethally irradiated zebrafish embryos. In addition, direct NF-kappaB inhibition reduced radiation-induced apoptosis in the central nervous system, abrogated aberrations in body axis development, restored metabolization and secretion of a reporter lipid through the gastrointestinal system, and improved renal clearance compromised by radiation. In contrast to amifostine, EP and CDDO-TFEA not only protected against but also mitigated radiation toxicity when given 1 to 2 hours postexposure. Finally, four additional IkappaB kinase inhibitors with distinct mechanisms of action similarly improved overall survival of lethally irradiated zebrafish embryos. In conclusion, inhibitors of canonical pathways to NF-kappaB activation may be useful in alleviating radiation toxicity in patients.
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