title: Influence of caloric restriction on constitutive expression of NF-κB in an experimental mouse astrocytoma.
abstract: 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  CR could be effective in reducing malignant brain tumor growth in part by inhibiting inflammation in the primary brain tumor.
authors.affiliation: Tumor Biology Program, Georgetown University Medical Center, Washington, DC, United States of America. mukherjp@bc.edu
authors.forename: Tiernan J
authors.initials: TJ
authors.lastname: Mulrooney
authors.forename: Jeremy
authors.initials: J
authors.lastname: Marsh
authors.forename: Ivan
authors.initials: I
authors.lastname: Urits
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Seyfried
authors.forename: Purna
authors.initials: P
authors.lastname: Mukherjee
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001254:Astrocytoma / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D031204:Caloric Restriction; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004273:DNA, Neoplasm / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D000097382:CD68 Molecule
chemical_list: D020155:3-Hydroxybutyric Acid; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001786:Blood Glucose; D002135:Calcium-Binding Proteins; D051546:Cyclooxygenase 2; D004273:DNA, Neoplasm; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D008840:Microfilament Proteins; D016328:NF-kappa B; C491049:Aif1 protein, mouse; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C077623:Ptgs2 protein, mouse