Tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces cell proliferation in normal human bronchial epithelial cells through NFκB activation and cyclin D1 up-regulation

Ho, Yuan Soon; Chen, Chien Ho; Wang, Ying Jan; Pestell, Richard G.; Albanese, Chris; Chang, Mei Chi; Jeng, Jiiang‐Huei; Lin, Shyr Yi; Liang, Yu Chih; Tseng, How; Lee, Wen Sen; Lin, Ju‐Li; Chu, Jan Show; Chen, Li Ching; Lee, Chia Hwa; Tso, Wei Ling; Lai, Yann Chwen; Wu, Chih Hsiung

doi:10.1016/j.taap.2004.09.019

Cited by 98 publications

(94 citation statements)

References 73 publications

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“…The role for NF-κB in mediating nicotine-dependent decrease of apoptosis has been demonstrated in lung cancer cells (Tsurutani et al, 2005). Nitrosamines stimulate normal human bronchial cell proliferation through activation of the NF-κB (Ho et al, 2005), and promote colon cancer growth in vitro via NF-κB that conveys the biological effect of α7-nAChR (Ye et al, 2004). Therefore, transcriptional and posttranscriptional activation of this signal transduction effector in oral KCs may play a key role in the pathogenesis of head and neck cancer by acting as tumor promoters that facilitate the outgrowth of cells with genetic damage.…”

Section: Discussionmentioning

confidence: 99%

“…Both environmental tobacco smoke and smokeless tobacco exhibit some of their pathobiologic effects at the cellular level through transactivation of NF-κB (Anto et al, 2002;Manna et al, 2006;Petro, 2003;Shen et al, 1996). The involvement of NF-κB in nicotine effects have been described in various types of normal and malignant cells (Cirillo et al, 2006;Ho et al, 2005;Lau et al, 2006;Manna et al, 2006;Tsurutani et al, 2005). It has been shown that stimulation of cells via nAChRs results in NF-κB activation (Heeschen et al, 2002), and that Ras/Raf-1/ERK pathway can mediate NF-κB activation (Chen et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Receptor-mediated tobacco toxicity: Alterations of the NF-κB expression and activity downstream of α7 nicotinic receptor in oral keratinocytes

et al. 2007

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To gain a mechanistic insight into nicotinic receptor-dependent morbidity of tobacco products in the oral cavity, we studied effects of exposures of normal human oral keratinocytes (KCs) for 24 h to environmental tobacco smoke (ETS) vs. equivalent concentration of pure nicotine. The exposed KCs showed a multifold increase of nuclear factor-κB (NF-κB) at the mRNA and protein levels, which could be significantly (p<0.05) diminished by α-bungarotoxin or transfection with anti-α7 small interfering RNA. An increased protein-binding activity of NF-κB also could be prevented by blocking α7 signaling. The use of pathway inhibitors demonstrated that the Ras/Raf-1/MEK1/ERK steps mediated α7-dependent upregulation of NF-κB. Thus, exposure of KCs to tobacco may lead to the pathobiologic effects via an intracellular signaling pathway downstream of α7 that proceeds through the Ras/Raf-1/MEK1/ERK steps leading to upregulated expression and transactivation of NF-κB.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Receptor-mediated tobacco toxicity: Alterations of the NF-κB expression and activity downstream of α7 nicotinic receptor in oral keratinocytes

et al. 2007

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“…It is evident from our data that EGCG inhibits CSC-induced activation of inflammatory markers, implying that EGCG can be useful in preventing the occurrence of an inflammatory environment apparently involved in the pathogenesis of cigarette smoke induced lung disease. NF-kB activation has been shown to result in the induction of the cyclin D1 gene (Ho et al, 2005). Also, increased cyclin D1 levels are found in different types of lung tumor tissues, as well as other tumors (Petty et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…As cyclin D1, MMP-9 and VEGF are NF-kB-regulated genes (Ho et al, 2005;Vlahos et al, 2006), we next investigated whether expression of these gene products is abrogated by EGCG. Immunoblot analysis showed that CSC exposure to NHBE cells resulted in an increase in the protein expression of cyclin D1 and MMP-9 and EGCG pretreatment resulted in a significant reduction in the expression of these proteins ( Figure 3).…”

Section: Egcg Treatment Of Nhbe Inhibits Csc-mediated Phosphorylationmentioning

confidence: 99%

Green tea polyphenol EGCG suppresses cigarette smoke condensate-induced NF-κB activation in normal human bronchial epithelial cells

et al. 2006

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Cigarette smoke is a powerful inducer of inflammatory responses resulting in disruption of major cellular pathways with transcriptional and genomic alterations driving the cells towards carcinogenesis. Cell culture and animal model studies indicate that (À)-epigallocatechin-3-gallate (EGCG), the major polyphenol present in green tea, possesses potent anti-inflammatory and antiproliferative activity capable of selectively inhibiting cell growth and inducing apoptosis in cancer cells without adversely affecting normal cells. Here, we demonstrate that EGCG pretreatment (20-80 lM) of normal human bronchial epithelial cells (NHBE) resulted in significant inhibition of cigarette smoke condensate (CSC)-induced cell proliferation. Nuclear factor-jB (NF-jB) controls the transcription of genes involved in immune and inflammatory responses. In most cells, NF-jB prevents apoptosis by mediating cell survival signals. Pretreatment of NHBE cells with EGCG suppressed CSC-induced phosphorylation of IjBa, and activation and nuclear translocation of NFjB/p65. NHBE cells transfected with a luciferase reporter plasmid containing an NF-jB-inducible promoter sequence showed an increased reporter activity after CSC exposure that was specifically inhibited by EGCG pretreatment. Immunoblot analysis showed that pretreatment of NHBE cells with EGCG resulted in a significant downregulation of NF-jB-regulated proteins cyclin D1, MMP-9, IL-8 and iNOS. EGCG pretreatment further inhibited CSC-induced phosphorylation of ERK1/2, JNK and p38 MAPKs and resulted in a decreased expression of PI3K, AKT and mTOR signaling molecules. Taken together, our data indicate that EGCG can suppress NF-jB activation as well as other pro-survival pathways such as PI3K/AKT/mTOR and MAPKs in NHBE cells, which may contribute to its ability to suppress inflammation, proliferation and angiogenesis induced by cigarette smoke.

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“…Especially, nitrosamines contained in cigarette smoke, such as NNK, are likely to mediate or aggravate pancreatic acinar cell damage by interfering with pancreatic regulation as well. NNK itself, which is formed during the curing process of tobacco, is a known carcinogen with the ability to induce pancreatic and other malignancies experimentally [51][52][53]. In humans, the pancreas must be exposed to NNK, because NNK has been detected in human pancreatic juice of smokers [6].…”

Section: Cigarette Smoke-induced Regulatory Eventsmentioning

confidence: 99%

Cigarette smoke-induced pancreatic damage—experimental data

Wittel

Hopt

Batra

2008

Langenbecks Arch Surg

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Tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces cell proliferation in normal human bronchial epithelial cells through NFκB activation and cyclin D1 up-regulation

Cited by 98 publications

References 73 publications

Receptor-mediated tobacco toxicity: Alterations of the NF-κB expression and activity downstream of α7 nicotinic receptor in oral keratinocytes

Receptor-mediated tobacco toxicity: Alterations of the NF-κB expression and activity downstream of α7 nicotinic receptor in oral keratinocytes

Green tea polyphenol EGCG suppresses cigarette smoke condensate-induced NF-κB activation in normal human bronchial epithelial cells

Cigarette smoke-induced pancreatic damage—experimental data

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