Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10895620 | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer | 2011 | 12 Pages |
Abstract
Cigarette smoking is a major cause of mortality and morbidity worldwide. Cyclooxygenase (COX) and its derived prostanoids, mainly including prostaglandin E2 (PGE2), thromboxane A2 (TxA2) and prostacyclin (PGI2), have well-known roles in cardiovascular disease and cancer, both of which are associated with cigarette smoking. This article is focused on the role of COX-2 pathway in smoke-related pathologies and cancer. Cigarette smoke exposure can induce COX-2 expression and activity, increase PGE2 and TxA2 release, and lead to an imbalance in PGI2 and TxA2 production in favor of the latter. It exerts pro-inflammatory effects in a PGE2-dependent manner, which contributes to carcinogenesis and tumor progression. TxA2 mediates other diverse biologic effects of cigarette smoking, such as platelet activation, cell contraction and angiogenesis, which may facilitate tumor growth and metastasis in smokers. Among cigarette smoke components, nicotine and its derived nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are the most potent carcinogens. COX-2 and PGE2 have been shown to play a pivotal role in many cancers associated with cigarette smoking, including cancers of lung, gastric and bladder, while the information for the role of TxA2 and PGI2 in smoke-associated cancers is limited. Recent findings from our group have revealed how NNK influences the TxA2 to promote the tumor growth. Better understanding in the above areas may help to generate new therapeutic protocols or to optimize the existing treatment strategy.
Keywords
PGI2NNKICAM-1ERKPGE2NNALPGISPPARpKaGPCRNATTXB2PGESHNSCCPKCNaBp38MAPKTxA2PLA2NNNCREBEGFRNSAIDSN′-nitrosoanabasineNF-κBMMPTSNAsTXASN′-nitrosonornicotineCOXTNFPCNAα7-nAChRTobacco-specific N-nitrosaminesPAHBLA4-(methylnitrosamino)-1-(3-pyridyl)-1-butanolcAMPG-protein-coupled receptorsCyclic adenosine monophosphateadenylate cyclaseproliferating-cell nuclear antigencyclooxygenasephospholipase A2Arachidonic acidinterferonIFNinterleukinSelective COX-2 inhibitorsBronchoalveolarSCLCthromboxane B2Thromboxane A2thromboxane synthaseNon-steroidal anti-inflammatory drugsCancerNSCLCSmall cell lung cancerNon-small cell lung cancerProstacyclin synthaseVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)tumor necrosis factornuclear factor kappa Bmatrix metallopeptidaseMEKcigarette smokingintercellular adhesion molecule-1NicotinePolycyclic aromatic hydrocarbonsprotein kinase AProtein kinase Cp38 mitogen-activated protein kinasemitogen-activated protein kinase kinaseprostacyclinprostaglandin E receptorprostaglandin E synthaseProstaglandin E2Head and neck squamous cell carcinomaCoxibsextracellular signal-regulated kinasesthromboxane A2 receptorEpidermal growth factor receptorPeroxisome-proliferator-activated receptorProstacyclin receptor
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Authors
Run-Yue Huang, George G. Chen,