title: Cigarette smoking, cyclooxygenase-2 pathway and cancer.
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.
authors.affiliation: Department of Surgery, The Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
authors.forename: Run-Yue
authors.initials: RY
authors.lastname: Huang
authors.forename: George G
authors.initials: GG
authors.lastname: Chen
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000502:physiology*; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000209:etiology; D011379:Prognosis; D015398:Signal Transduction; D012907:Smoking / Q000009:adverse effects*
chemical_list: D051546:Cyclooxygenase 2