title: Dietary curcumin increases antioxidant defenses in lung, ameliorates radiation-induced pulmonary fibrosis, and improves survival in mice.
abstract: The effectiveness of lung radiotherapy is limited by radiation tolerance of normal tissues and by the intrinsic radiosensitivity of lung cancer cells. The chemopreventive agent curcumin has known antioxidant and tumor cell radiosensitizing properties. Its usefulness in preventing radiation-induced pneumonopathy has not been tested previously. We evaluated dietary curcumin in radiation-induced pneumonopathy and lung tumor regression in a murine model. Mice were given 1% or 5% (w/w) dietary curcumin or control diet prior to irradiation and for the duration of the experiment. Lungs were evaluated at 3 weeks after irradiation for acute lung injury and inflammation by evaluating bronchoalveolar lavage (BAL) fluid content for proteins, neutrophils and at 4 months for pulmonary fibrosis. In a separate series of experiments, an orthotopic model of lung cancer using intravenously injected Lewis lung carcinoma (LLC) cells was used to exclude possible tumor radioprotection by dietary curcumin. In vitro, curcumin boosted antioxidant defenses by increasing heme oxygenase 1 (HO-1) levels in primary lung endothelial and fibroblast cells and blocked radiation-induced generation of reactive oxygen species (ROS). Dietary curcumin significantly increased HO-1 in lungs as early as after 1 week of feeding, coinciding with a steady-state level of curcumin in plasma. Although both 1% and 5% w/w dietary curcumin exerted physiological changes in lung tissues by significantly decreasing LPS-induced TNF-alpha production in lungs, only 5% dietary curcumin significantly improved survival of mice after irradiation and decreased radiation-induced lung fibrosis. Importantly, dietary curcumin did not protect LLC pulmonary metastases from radiation killing. Thus dietary curcumin ameliorates radiation-induced pulmonary fibrosis and increases mouse survival while not impairing tumor cell killing by radiation.
authors.affiliation: Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Lee
authors.forename: Paul A
authors.initials: PA
authors.lastname: Kinniry
authors.forename: Evguenia
authors.initials: E
authors.lastname: Arguiri
authors.forename: Matthew
authors.initials: M
authors.lastname: Serota
authors.forename: Stathis
authors.initials: S
authors.lastname: Kanterakis
authors.forename: Shampa
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Charalambos C
authors.initials: CC
authors.lastname: Solomides
authors.forename: Prashanthi
authors.initials: P
authors.lastname: Javvadi
authors.forename: Constantinos
authors.initials: C
authors.lastname: Koumenis
authors.forename: Keith A
authors.initials: KA
authors.lastname: Cengel
authors.forename: Melpo
authors.initials: M
authors.lastname: Christofidou-Solomidou
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid; D018827:Carcinoma, Lewis Lung / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000517:prevention & control*; D011832:Radiation Injuries / Q000517:prevention & control*; D021241:Spectrometry, Mass, Electrospray Ionization; D016019:Survival Analysis; D053719:Tandem Mass Spectrometry
chemical_list: D000975:Antioxidants; D006419:Heme Oxygenase (Decyclizing); D003474:Curcumin