Nicotine and lung cancer

Abstract

Tobacco use in cancer patients is associated with increased cancer treatment failure and decreased survival. Nicotine is one of over 7,000 compounds in tobacco smoke and nicotine is the principal chemical associated with addiction. The purpose of this article is to review the tumor promoting activities of nicotine. Nicotine and its metabolites can promote tumor growth through increased proliferation, angiogenesis, migration, invasion, epithelial to mesenchymal transition, and stimulation of autocrine loops associated with tumor growth. Furthermore, nicotine can decrease the biologic effectiveness of conventional cancer treatments such as chemotherapy and radiotherapy. Common mechanisms appear to involve activation of nicotinic acetylcholine receptors and beta-adrenergic receptors leading to downstream activation of parallel signal transduction pathways that facilitate tumor progression and resistance to treatment. Data suggest that nicotine may be an important mechanism by which tobacco promotes tumor development, progression, and resistance to cancer treatment.

Electronic Nicotine Delivery Systems: A Policy Statement from the American Association for Cancer Research and the American Society of Clinical Oncology

“…No controlled trials have examined the efficacy and safety of ENDS in cancer patients treated with surgery, chemotherapy, or radiotherapy. The potential interactions of ENDS with cytotoxic cancer therapeutics are also unknown, and there is in vitro evidence that nicotine stimulates proliferation, migration, invasion, and angiogenesis and decreases cancer cell death from irradiation and chemotherapy, raising concern as to whether prolonged ENDS use might have similar effects in patients with cancer (78). Moreover, researchers have found that human bronchial cells grown in medium exposed to e-cigarette aerosol showed a similar pattern of gene expression to those grown in medium exposed to tobacco smoke (79).…”

Nicotine enhances hepatocyte growth factor-mediated lung cancer cell migration by activating the α7 nicotine acetylcholine receptor and phosphoinositide kinase-3-dependent pathway

“…Among them, α7-nAchR has been demonstrated to be expressed in cancer cells, including lung cancer A549 cells (24,25). Lending support to the demonstration of cross-talk between nicotine/α7-nAchR and HGF/c-Met in the present study, previous studies have established that nicotine/α7-nAchR cross-talks with the downstream signaling of various growth factors, including epithelial cell growth factor, basic fibroblast growth factor and vascular endothelial cell growth factor, promoting cancer cell proliferation (4,17,24). However, the mechanisms underlying signal crosstalk are complex.…”

“…Cumulative evidence suggests that nicotine may have a broad spectrum of tumor-promoting activities, which include increasing cell proliferation, invasion, EMT and angiogenesis (4). The present study provides an insight into the mechanism of the promotion of tumor cell activities initiated by nicotine, by demonstrating how nicotine-modulated growth factor-mediated signal transduction leads to increased cell motility, a vital step in cancer invasion and metastasis.…”

“…Cigarette smoke contains numerous carcinogens, of which, polycyclic aromatic hydrocarbons and the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol, are likely to serve major roles (3). However, recent evidence suggests that cigarette smoking not only promotes lung carcinogenesis, but that it also promotes the progression of lung cancer (4). For example, continued smoking during lung cancer treatment has been associated with decreased survival (5), while smoking cessation during the treatment improves the therapeutic outcome (6).…”

“…Whilst it does not exert direct carcinogenic activity, nicotine is commonly accepted instead as a tumor promoter (4). Recent evidence suggests that the tumor-promoting effects of nicotine result in increased proliferation, invasion, mesenchymal transition (EMT) and angiogenesis, and decreased cell death and apoptosis (4,(9)(10)(11)(12)(13)(14)(15)(16)(17).…”