Nicotine, Lung and Cancer (original) (raw)
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… Journal of Cancer, 2009
Cigarette smoking is strongly correlated with the onset of non-small cell lung cancer (NSCLC). Nicotine, an active component of cigarettes, has been found to induce proliferation of lung cancer cell lines. In addition, nicotine can induce angiogenesis and confer resistance to apoptosis. All these events are mediated through the nicotinic acetylcholine receptors (nAChRs) on lung cancer cells. In the present study we demonstrate that nicotine can promote anchorage-independent growth in NSCLCs. In addition, nicotine also induced morphological changes characteristic of a migratory, invasive phenotype in NSCLCs on collagen gel. These morphological changes were similar to those induced by the pro-migratory growth factor VEGF. The pro-invasive effects of nicotine were mediated by α7-nAChRs on NSCLCs. RT-PCR analysis showed that the α7-nAChRs were also expressed on human breast cancer and pancreatic cancer cell lines. Nicotine was found to promote proliferation and invasion in human breast cancer. The pro-invasive effects of nicotine were mediated via a nAChR, Src and calcium dependent signaling pathway in breast cancer cells. In a similar fashion nicotine could also induce proliferation and invasion of Aspc1 pancreatic cancer cells. Most importantly, nicotine could induce changes in gene expression consistent with epithelial to mesenchymal transition, characterized by reduction of epithelial markers like E-cadherin expression, ZO-1 staining and concomitant increase in levels of mesenchymal proteins like vimentin and fibronectin in human breast and lung cancer cells. Therefore, it is probable that the ability of nicotine to induce invasion and EMT may contribute to the progression of breast and lung cancers.
Nicotine promotes tumor growth and metastasis in mouse models of lung cancer
PLoS One, 2009
Background: Nicotine is the major addictive component of tobacco smoke. Although nicotine is generally thought to have limited ability to initiate cancer, it can induce cell proliferation and angiogenesis in a variety of systems. These properties might enable nicotine to facilitate the growth of tumors already initiated. Here we show that nicotine significantly promotes the progression and metastasis of tumors in mouse models of lung cancer. This effect was observed when nicotine was administered through intraperitoneal injections, or through over-the-counter transdermal patches.
Journal of Surgical Research, 2012
Nicotine a7-Nicotinic acetylcholine receptor (a7-nAChR) Colon cancer cells Apoptosis Surviving P-Bcl2 a b s t r a c t Background: Colorectal cancer is one of the leading causes of cancer-related death throughout the world, and the risk to develop this malignant disease seems to be associated with long-term cigarette smoking. Nicotine, one of the major components of cigarette smoking, can stimulate cell proliferation and suppress apoptosis both in normal cells and in several human cancer cell lines derived from various organs. However, although nicotine appears to have a role in stimulating cell proliferation of colon cancer cells, there is no information on its role in inhibiting apoptosis in these cells. Materials and methods: Human colorectal cancer cell lines Caco-2 and HCT-8 were treated with 1 mM nicotine alone or in combination with 1 mM a-BTX in complete or in serum free medium. Cell proliferation and apoptosis were determined by cell count performed with a cell counter and by cytofluorimetric assay respectively. PI3K/Akt and PKC/ERK1/2 pathways, survivin, and P-Bcl2 (Ser70) were investigated by Western blot analysis. Results: Nicotine induced an increase in cell proliferation and a decrease of apoptosis in Caco-2 and HCT-8 cells. Both cell growth and apoptosis appear to be mediated by a7nicotinic acetylcholine receptors, since treatment with a-Bungarotoxin inhibited these processes. Nicotine induced a statistically significant increase in the expression of PI3K and in P-Akt/Akt ratio as well as in the expression of PKC, ERK1/2, survivin, and P-Bcl2 (Ser70) in both cell lines. Conclusions: Nicotine, contained in cigarette smoking, could participate in colon cancer development and progression by stimulating cell proliferation and suppressing physiological apoptosis. ª
The effects of cigarette smoking extracts on cell cycle and tumor spread: novel evidence
Future Science OA
Cigarette smoking is a major preventable risk factor for lung cancer, contributing to lung cancer progression and metastasis. Moreover, cigarette smoking correlates with increased metastasis frequency of pancreatic, breast and bladder cancer. The aim of this review was to examine the role of cigarette smoke extract in cell cycle and cancer progression. Clinical impact and the effects of cigarette smoke extract on carcinogenesis are discussed. 98 of the over 5000 chemicals in tobacco smoke are known carcinogens that can act on cancer genes such as K-RAS and p53. Through various mechanisms these compounds can activate molecules involved in the cell cycle, such as cyclins, and molecules involved in apoptosis and autophagy, such as Beclin-1 or LC3B. A search of the literature, including in vitro and in vivo studies, was carried out and the results summarized. Lay abstract: There is evidence of cancerogenic effects of cigarette smoke compounds. Cigarette smoke extract is a tobacco condensate obtained by filtration processes. Studies have shown that it can modify the cell cycle, inducing uncontrolled cell proliferation. This effect occurs through activation of genetic and epigenetic pathways and increasing the expression of proteins involved in inflammation. The pathways activated by cigarette smoke extract open up opportunities for researchers to develop new targeted therapies toward the specific molecules involved. Furthermore, the effects exerted by cigarette smoke extract on normal epithelial cells hold potential for use in the development of prevention medicine and early cancer diagnosis.
Low-Dose Nicotine Activates EGFR Signaling via α5-nAChR and Promotes Lung Adenocarcinoma Progression
International Journal of Molecular Sciences, 2020
Nicotine in tobacco smoke is considered carcinogenic in several malignancies including lung cancer. The high incidence of lung adenocarcinoma (LAC) in non-smokers, however, remains unexplained. Although LAC has long been less associated with smoking behavior based on previous epidemiological correlation studies, the effect of environmental smoke contributing to low-dose nicotine exposure in non-smoking population could be underestimated. Here we provide experimental evidence of how low-dose nicotine promotes LAC growth in vitro and in vivo. Screening of nicotinic acetylcholine receptor subunits in lung cancer cell lines demonstrated a particularly high expression level of nicotinic acetylcholine receptor subunit α5 (α 5-nAChR) in LAC cell lines. Clinical specimen analysis revealed up-regulation of α 5-nAChR in LAC tumor tissues compared to non-tumor counterparts. In LAC cell lines α 5-nAChR interacts with epidermal growth factor receptor (EGFR), positively regulates EGFR pathway, en...