Influence of Caloric Restriction on Constitutive Expression of NF-κB in an Experimental Mouse Astrocytoma
Open accessAbstract
BACKGROUND: Many of the current standard therapies employed for the management of primary malignant brain cancers are largely viewed as palliative, ultimately because these conventional strategies have been shown, in many instances, to decrease patient quality of life while only offering a modest increase in the length of survival. We propose that caloric restriction (CR) is an alternative metabolic therapy for brain cancer management that will not only improve survival but also reduce the morbidity associated with disease. Although we have shown that CR manages tumor growth and improves survival through multiple molecular and biochemical mechanisms, little information is known about the role that CR plays in modulating inflammation in brain tumor tissue. METHODOLOGY/PRINCIPAL FINDINGS: Phosphorylation and activation of nuclear factor κB (NF-κB) results in the transactivation of many genes including those encoding cycloxygenase-2 (COX-2) and allograft inflammatory factor-1 (AIF-1), both of which are proteins that are primarily expressed by inflammatory and malignant cancer cells. COX-2 has been shown to enhance inflammation and promote tumor cell survival in both in vitro and in vivo studies. In the current report, we demonstrate that the p65 subunit of NF-κB was expressed constitutively in the CT-2A tumor compared with contra-lateral normal brain tissue, and we also show that CR reduces (i) the phosphorylation and degree of transcriptional activation of the NF-κB-dependent genes COX-2 and AIF-1 in tumor tissue, as well as (ii) the expression of proinflammatory markers lying downstream of NF-κB in the CT-2A malignant mouse astrocytoma, [e.g. macrophage inflammatory protein-2 (MIP-2)]. On the whole, our date indicate that the NF-κB inflammatory pathway is constitutively activated in the CT-2A astrocytoma and that CR targets this pathway and inflammation. CONCLUSION: CR could be effective in reducing malignant brain tumor growth in part by inhibiting inflammation in the primary brain tumor.
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Dietary restriction reduces phosphorylation and activity of NF-κB in the brain of a mouse model of experimental astrocytoma.
“Besides regulating expression of NF-κB, DR also reduced phosphorylation and activity of NF-κB in the brain of a mouse model of experimental astrocytoma [148].”
From Dietary Restriction and Neuroinflammation: A Potential Mechanistic Link (2019) · cites this paper as [148]
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“Besides regulating expression of NF-κB, DR also reduced phosphorylation and activity of NF-κB in the brain of a mouse model of experimental astrocytoma [148].”
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- Authors
- Mulrooney, T. J., Marsh, J., Urits, I., Seyfried, T. N., & Mukherjee, P.
- Affiliations
- Georgetown University Medical Center (US)
- Albert Einstein College of Medicine (US)
- Boston College (US)
- Corresponding author
- Mukherjee, Purna
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-03-30
- Volume
- 6
- Issue
- 3
- Pages
- e18085
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3068150
- OpenAlex
- W2086693940
- Cited by
- 75
- References
- 108
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 7 · 2021: 6 · 2020: 11 · 2019: 5 · 2018: 4 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 9 · 2013: 2 · 2012: 5
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Boston College
- Harvard University
- National Institutes of Health
- National Cancer Institute (CA-102135, R01CA102135)
- National Institute of Neurological Disorders and Stroke (R01NS055195, NS-055195, R56NS055195)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Keywords
- caloric restriction, NF-κB, astrocytoma, cyclooxygenase-2, allograft inflammatory factor-1, tumor inflammation, p65 phosphorylation, CXCL2, metabolic therapy, brain cancer
- MeSH terms
- CD68 Molecule, Animals, Astrocytoma, Blood Glucose, Body Weight, Brain, Calcium-Binding Proteins, Cell Nucleus, Cytosol, DNA, Neoplasm, Male, Mice, Inbred C57BL, Microfilament Proteins, Phosphorylation, Promoter Regions, Genetic, Protein Binding, Blotting, Western, Antigens, Differentiation, Myelomonocytic, Antigens, CD, NF-kappa B, Inflammation Mediators, 3-Hydroxybutyric Acid, I-kappa B Proteins, Caloric Restriction, Cell Proliferation, Mice, Cyclooxygenase 2
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