Dietary Curcumin Increases Antioxidant Defenses in Lung, Ameliorates Radiation-Induced Pulmonary Fibrosis, and Improves Survival in Mice

被引:125
作者
Lee, James C. [1 ]
Kinniry, Paul A. [1 ]
Arguiri, Evguenia [1 ]
Serota, Matthew [1 ]
Kanterakis, Stathis [1 ]
Chatterjee, Shampa [2 ]
Solomides, Charalambos C. [4 ]
Javvadi, Prashanthi [3 ]
Koumenis, Constantinos [3 ]
Cengel, Keith A. [3 ]
Christofidou-Solomidou, Melpo [1 ]
机构
[1] Univ Penn, Dept Med, Pulm Allergy & Crit Care Div, Med Ctr, Philadelphia, PA 19104 USA
[2] Univ Penn, Med Ctr, Dept Pharmacol, Philadelphia, PA 19104 USA
[3] Univ Penn, Med Ctr, Dept Radiat Oncol, Philadelphia, PA 19104 USA
[4] Temple Univ Hosp & Med Sch, Dept Pathol, Philadelphia, PA 19104 USA
关键词
NF-KAPPA-B; SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; GENE-EXPRESSION; MOUSE MODEL; INJURY; DIFERULOYLMETHANE; RADIOPROTECTION; ACTIVATION; INHIBITION;
D O I
10.1667/RR1522.1
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. (C) 2010 by Radiation Research Society
引用
收藏
页码:590 / 601
页数:12
相关论文
共 48 条
[1]   Role for platelet-endothelial cell adhesion molecule-1 in macrophage Fcγ receptor function [J].
Albelda, SM ;
Lau, KC ;
Chien, P ;
Huang, ZY ;
Arguiris, E ;
Bohen, A ;
Sun, J ;
Billet, JA ;
Christofidou-Solomidou, M ;
Indik, ZK ;
Schreiber, AD .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2004, 31 (02) :246-255
[2]   Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature [J].
Anand, Preetha ;
Thomas, Sherin G. ;
Kunnumakkara, Ajaikumar B. ;
Sundaram, Chitra ;
Harikumar, Kuzhuvelil B. ;
Sung, Bokyung ;
Tharakan, Sheeja T. ;
Misra, Krishna ;
Priyadarsini, Indira K. ;
Rajasekharan, Kallikat N. ;
Aggarwal, Bharat B. .
BIOCHEMICAL PHARMACOLOGY, 2008, 76 (11) :1590-1611
[3]   Curcumin and cancer: An "old-age" disease with an "age-old" solution [J].
Anand, Preetha ;
Sundaram, Chitra ;
Jhurani, Sonia ;
Kunnumakkara, Ajaikumar B. ;
Aggarwal, Bharat B. .
CANCER LETTERS, 2008, 267 (01) :133-164
[4]   Reactive oxygen species scavengers attenuate endotoxin-induced impairment of hypoxic pulmonary vasoconstriction in mice [J].
Baboolal, HA ;
Ichinose, F ;
Ullrich, R ;
Kawai, N ;
Bloch, KD ;
Zapol, WM .
ANESTHESIOLOGY, 2002, 97 (05) :1227-1233
[5]   Curcurnin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element [J].
Balogun, E ;
Hoque, M ;
Gong, PF ;
Killeen, E ;
Green, CJ ;
Foresti, R ;
Alam, J ;
Motterlini, R .
BIOCHEMICAL JOURNAL, 2003, 371 :887-895
[6]   ESTABLISHMENT OF A CLONED LINE OF LEWIS LUNG-CARCINOMA CELLS ADAPTED TO CELL-CULTURE [J].
BERTRAM, JS ;
JANIK, P .
CANCER LETTERS, 1980, 11 (01) :63-73
[7]  
Bierhaus A, 1997, THROMB HAEMOSTASIS, V77, P772
[8]   Oncogenic K-Ras signals through epidermal growth factor receptor and wild-type H-Ras to promote radiation survival in pancreatic and colorectal carcinoma cells [J].
Cengel, Keith A. ;
Voong, K. Rahn ;
Chandrasekaran, Sanjay ;
Maggiorella, Laurence ;
Brunner, Thomas B. ;
Stanbridge, Eric ;
Kao, Gary D. ;
McKenna, W. Gillies ;
Bernhard, Eric J. .
NEOPLASIA, 2007, 9 (04) :341-348
[9]   KATP channels are an important component of the shear-sensing mechanism in the pulmonary microvasculature [J].
Chatterjee, S. ;
Levitan, I. ;
Wei, Z. ;
Fisher, A. B. .
MICROCIRCULATION, 2006, 13 (08) :633-644
[10]   Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway by curcumin [J].
Chen, YR ;
Tan, TH .
ONCOGENE, 1998, 17 (02) :173-178