| Title | Curcumin inhibits tumor proliferation induced by neutrophil elastase through the upregulation of alpha 1-antitrypsin in lung cancer |
| Authors | Xu, Yan Zhang, Jingjie Han, Jing Pan, Xueyang Cao, Yajun Guo, Hao Pan, Yan An, Yu Li, Xuejun |
| Affiliation | Peking Univ, State Key Lab Nat & Biomimet Drugs, Dept Pharmacol, Sch Basic Med Sci, Beijing 100191, Peoples R China. Peking Univ, Inst Syst Biomed, Beijing 100191, Peoples R China. Shihezi Univ, Key Lab Xinjiang Phytomed Resources Modernizat TC, Sch Pharmaceut Sci, Shihezi 832002, Xinjiang, Peoples R China. Peking Univ, State Key Lab Nat & Biomimet Drugs, Dept Pharmacol, Sch Basic Med Sci, 38 Xueyuan Rd, Beijing 100191, Peoples R China. |
| Keywords | Curcumin Tumor proliferation alpha 1-antitrypsin Neutrophil elastase FACTOR-KAPPA-B NONSMALL CELL LUNG PANCREATIC-CANCER OVARIAN-CANCER ANGIOGENESIS APOPTOSIS INFLAMMATION CARCINOMA MECHANISM GENE |
| Issue Date | 2012 |
| Publisher | molecular oncology |
| Citation | MOLECULAR ONCOLOGY.2012,6,(4),405-417. |
| Abstract | Lung carcinogenesis is a complex process in an unregulated inflammatory environment. Curcumin has been extensively investigated as a multi-target anti-tumor and anti-inflammation compound. In this paper, we demonstrate a novel inflammation-related mechanism for curcumin-induced inhibition of lung tumor growth. We found that neutrophil elastase, an important regulator of inflammatory processes, directly triggered tumor cell proliferation in human lung adenocarcinoma A549 cells, and curcumin could completely suppress the excess tumor proliferation induced by neutrophil elastase. alpha 1-antitrypsin is synthesized by tumor cells and is the natural inhibitor of neutrophil elastase. We found that curcumin counteracted the decrease of alpha 1-antitrypsin induced by neutrophil elastase by inducing the promoter activity of alpha 1-antitrypsin and promoting its expression in A549 cells. The inhibition of neutrophil elastase-induced proliferation by curcumin was dependent on the PI3K/Akt pathway. Knockdown of alpha 1-antitrypsin by siRNA further enhanced the tumor cell proliferation induced by neutrophil elastase and significantly blocked the anti-proliferation effect of curcumin against neutrophil elastase. Curcumin remarkably inhibited the primary tumor growth of Lewis lung carcinoma (LLC) in C57BL/6 mice. We further showed that curcumin upregulated the level of alpha 1-antitrypsin in primary tumor tissue by promoting its local expression, and the protein level of neutrophil elastase in tumor tissue was obviously decreased in mice treated with curcumin. Overall, our results suggest that neutrophil elastase and alpha 1-antitrypsin play important roles in modulating lung tumor proliferation in inflammatory microenvironment and curcumin inhibits neutrophil elastase-induced tumor proliferation via upregulating alpha 1-antitrypsin expression in vitro and in vivo. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/156603 |
| ISSN | 1574-7891 |
| DOI | 10.1016/j.molonc.2012.03.005 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 药学院 天然药物与仿生药物国家重点实验室 |
