Mitochondrial reactive oxygen species mediates nicotine-induced hypoxia-inducible factor-1α expression in human non-small cell lung cancer cells

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1822

Article

Guo, Lili¹  Li, Lin¹  Wang, Weiqiang¹  Pan, Zhenhua¹  Zhou, Qinghua¹  Wu, Zhihao¹ 

[1] Tianjin Med Univ Gen Hosp, Tianjin Key Lab Lung Canc Metastasis & Tumor Micr, Tianjin Lung Canc Inst, Tianjin 300052, Peoples R China

关键词: Nicotine;    Hypoxia-inducible factor 1 alpha;    Mitochondria;    Reactive oxygen species;    Lung cancer metastasis;   

DOI  :  10.1016/j.bbadis.2012.02.004

来源: Elsevier

【 摘 要 】

Cigarette smoking is not only a documented risk for lung carcinogenesis but also promotes lung cancer development. Nicotine, a major component of cigarette smoke but not a carcinogen by itself, has been found to induce proliferation, invasion and metastasis of non-small cell lung cancer (NSCLC). Here we reported that proinvasive effect of nicotine is analogous to that of hypoxia and involves stabilization and activation of hypoxia-inducible factor (HIF)-1 alpha, a key factor in determining the presence of HIF-1 and expression of its downstream metastasis-associated genes. Furthermore, nicotine-induced upregulation of HIF-1 alpha was dependent on mitochondria-derived reactive oxygen species (ROS). Ecotopic expression of mitochondrial targeted catalase effectively prevented nicotine-induced accumulation of HIF-1 alpha protein. In addition, we demonstrated that the effect of nicotine in upregulation of HIF-1 alpha was mediated by Dihydro-beta-erythroidine (Dh beta E)-sensitive nicotine acetylcholine receptors (nAChRs) and required synergistic cooperation of Akt and mitogen-activated protein kinase (MAPK) pathways. These results suggest that exposure to nicotine could mimic effects of hypoxia to stimulate HIF-1 alpha accumulation and activity that might underlie the high metastatic potential of lung cancer. (C) 2012 Elsevier B.V. All rights reserved.

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