Nicotine Induces Resistance to Chemotherapy in Nasal Epithelial Cancer

Shen, Tianjie; Le, Wei; Yee, Allison M; Kamdar, Opal; Hwang, Peter H.; Upadhyay, Daya

doi:10.2500/ajra.2010.24.3456

Cited by 39 publications

(23 citation statements)

References 20 publications

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“…Nicotine was found to reduce the senescence of endothelial progenitor cells by increasing telomerase activity via Akt signaling [43]. In addition, the anti-apoptotic effects of nicotine have been shown to be partly mediated by PI3K/Akt and MAPK in nasal epithelial cancer [44]. It is possible that nicotine, which has been shown to target NF-kappaB [21], may also work through pro-inflammatory pathways to promote stem cell properties.…”

Section: Discussionmentioning

confidence: 99%

Nicotine Promotes Acquisition of Stem Cell and Epithelial-to-Mesenchymal Properties in Head and Neck Squamous Cell Carcinoma

Kiang

Wang‐Rodriguez

et al. 2012

PLoS ONE

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The ability of nicotine to enhance the malignancy of cancer cells is known; however, the possibility that nicotine could regulate a cancer stem cell phenotype remains to be well-established. In this study we sought to determine whether long-term exposure to nicotine could promote cancer stem cell-like properties in two head and neck squamous cell carcinoma cell lines, UMSCC-10B and HN-1. Nicotine treatment induced epithelial-to-mesenchymal transition (EMT) in both cell lines by repressing E-cadherin expression, and led to the induction of stem cell markers Oct-4, Nanog, CD44 and BMI-1, which was reversed upon ectopic re-expression of E-cadherin. Nicotine-treated cells formed spheres at a higher efficiency than non-treated cells, formed larger tumors when injected into mice, and formed tumors with 4-fold greater efficiency compared to control cells when injected at limiting doses. Consistent with previous literature, nicotine-treated cells demonstrated a greater capacity for survival and also a higher tendency to invade. Comparison of microRNA profiles between nicotine and control cells revealed the upregulation of miR-9, a repressor of E-cadherin, and the downregulation of miR-101, a repressor of EZH2. Taken together, these results suggest that nicotine may play a critical role in the development of tobacco-induced cancers by regulating cancer stem cell characteristics, and that these effects are likely mediated through EMT-promoting, microRNA-mediated pathways. Further characterization of such pathways remains a promising avenue for the understanding and treatment of tobacco-related cancers.

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Section: Discussionmentioning

confidence: 99%

Nicotine Promotes Acquisition of Stem Cell and Epithelial-to-Mesenchymal Properties in Head and Neck Squamous Cell Carcinoma

Kiang

Wang‐Rodriguez

et al. 2012

PLoS ONE

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“…However, pre-clinical models have shown that nicotine can activate components of the PI3K, MAPK and Src pathways that increase lung cancer cell proliferation, survival and migration (9–12). Activation of these pathways by nicotine can also partially transform epithelial cells, induce an epithelial-mesenchymal transition (EMT), and increase chemotherapeutic resistance (9, 13, 14). When extrapolated to former smokers, these data have raised the possibility that NRT might contribute to adverse clinical outcomes.…”

Section: Introductionmentioning

confidence: 99%

Nicotine Does Not Enhance Tumorigenesis in MutantK-Ras–Driven Mouse Models of Lung Cancer

Maier¹,

Hollander²,

Hobbs³

et al. 2011

Cancer Prevention Research

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Smoking is the leading cause of preventable cancer deaths in the United States. Nicotine replacement therapies (NRT) have been developed to aid in smoking cessation, which decreases lung cancer incidence. However, the safety of NRT is controversial because numerous preclinical studies have shown that nicotine enhances tumor cell growth in vitro and in vivo. We modeled NRT in mice to determine the effects of physiological levels of nicotine on lung tumor formation, tumor growth or metastasis. Nicotine administered in drinking water did not enhance lung tumorigenesis after treatment with the tobacco carcinogen, NNK. Tumors that develop in this model have mutations in K-ras, which is a commonly observed in smoking-related, human lung adenocarcinomas. In a transgenic model of mutant K-ras-driven lung cancer, nicotine did not increase tumor number or size, and did not affect overall survival. Likewise, in a syngeneic model of lung cancer cell lines derived from NNK-treated mice, oral nicotine did not enhance tumor growth or metastasis. These data show that nicotine does not enhance lung tumorigenesis when given to achieve levels comparable to those of NRT, suggesting that nicotine has a dose threshold, below which it has no appreciable effect. These studies are consistent with epidemiological data showing that NRT does not enhance lung cancer risk in former smokers.

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“…[10][11][12][13] These effects of nicotine are mediated by nicotinic acetylcholine receptors (nAChRs) that are widely expressed in the lung as well as the brain and neuromuscular junctions. 5,10,[13][14][15] Nicotine also reduces the effectiveness of cancer chemotherapy 14,16,17 ; however, the mechanism by which this occurs remains unclear.…”

mentioning

confidence: 99%

Nicotine Induces Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor by α1 Nicotinic Acetylcholine Receptor–Mediated Activation in PC9 Cells

Wang

Takayama

Tanaka

et al. 2013

Journal of Thoracic Oncology

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Nicotine Induces Resistance to Chemotherapy in Nasal Epithelial Cancer

Abstract: Nicotine inhibits chemotherapy-induced apoptosis in NC via the AKT and MAPK-mediated signaling pathways. We speculate that nicotine may play a role in oncogenesis and resistance to cancer therapy in NC.

Cited by 39 publications

References 20 publications

Nicotine Promotes Acquisition of Stem Cell and Epithelial-to-Mesenchymal Properties in Head and Neck Squamous Cell Carcinoma

Nicotine Promotes Acquisition of Stem Cell and Epithelial-to-Mesenchymal Properties in Head and Neck Squamous Cell Carcinoma

Nicotine Does Not Enhance Tumorigenesis in MutantK-Ras–Driven Mouse Models of Lung Cancer

Nicotine Induces Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor by α1 Nicotinic Acetylcholine Receptor–Mediated Activation in PC9 Cells

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