Effects of tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on the activation of ERK1/2 MAP kinases and the proliferation of human mammary epithelial cells

Chen, Zhibo; Liu, Chang; Chen, Feng-Qing; Li, Shanyu; Qiao, Li; Liu, Lanying

doi:10.1016/j.etap.2006.04.001

Cited by 19 publications

(11 citation statements)

References 32 publications

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“…Herein, it is important to highlight that WPS did not significantly affect the total expression of Erk1/Erk2. Indeed, these data are consistent with previous works regarding cigarette smoking in relation with EMT and Erk1/Erk2 activation, as well as E-cadherin deregulation in various types of human cancer cells including breast [ 19 , 21 , 44 – 46 ]. Thus, the present study show that Erk1/Erk2 activation is one of the pathways via which WPS can enhance cancer progression and initiate metastasis.…”

Section: Discussionsupporting

confidence: 92%

Water-pipe smoking promotes epithelial–mesenchymal transition and invasion of human breast cancer cells via ERK1/ERK2 pathways

et al. 2018

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BackgroundWith the increasing popularity of water-pipe smoking (WPS), it is critical to comprehend how WPS may affect women’s health. The main goal of this study is to identify the potential outcome of WPS on human breast cancer progression.MethodsTwo breast cancer cell lines, MCF7 and BT20, were used in this investigation. We explored the outcome of WPS on cell morphology and cell invasion using inverted microscope and Biocoat Matrigel invasion chambers. On the other hand, Western blot was employed to study the expression patterns of key control genes of cell adhesion and invasion.ResultsOur data reveal that WPS induces epithelial–mesenchymal transition (EMT) of MCF7 and BT20 breast cancer cell lines; thus, WPS enhances cell invasion ability of both cell lines in comparison with their matched controls. More significantly, WPS provokes a down- and up-regulation of E-cadherin and focal adhesion kinase (FAK), respectively, which are important key regulators of cancer progression genes. Finally, our data point out that WPS incites the activation of Erk1/Erk2, which could be behind the stimulation of EMT and invasion as well as the deregulation of E-cadherin and FAK expression.ConclusionOur data show, for the first time, that WPS initiates EMT and stimulates cell invasion of breast cancer cells, which could incite metastatic development in breast cancer patients. Thus, we believe that further studies, both in vitro and in vivo, are required to elucidate the pathogenic outcome of WPS on cancer progression of several human carcinomas including breast.

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Section: Discussionsupporting

confidence: 92%

Water-pipe smoking promotes epithelial–mesenchymal transition and invasion of human breast cancer cells via ERK1/ERK2 pathways

et al. 2018

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“…Although the tumorigenic action of nicotinic receptors induced by the NNK binding has been demonstrated in oral epithelial cells 41 – 44 , the role of beta-adrenergic signaling activated by the nitrosamine still need to be investigated. In other types of normal epithelial cells 45 , 46 , the tumorigenic action of beta-adrenergic receptors induced by NNK binding has already been evaluated. Beta-adrenergic receptors activated by the nitrosamine may mediate, for example, the levels of ERK1/2 MAP kinases in mammary cells 45 .…”

Section: Discussionmentioning

confidence: 99%

“…In other types of normal epithelial cells 45 , 46 , the tumorigenic action of beta-adrenergic receptors induced by NNK binding has already been evaluated. Beta-adrenergic receptors activated by the nitrosamine may mediate, for example, the levels of ERK1/2 MAP kinases in mammary cells 45 . In small airway cells, beta-adrenergic signaling activation by NNK can up-regulate ERK1/2 and ATF1/CREB phosphorylation via PKA 46 .…”

Section: Discussionmentioning

confidence: 99%

Stress hormones promote DNA damage in human oral keratinocytes

Valente

Cardoso

Kayahara

et al. 2021

Sci Rep

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Chronic stress increases the systemic levels of stress hormones norepinephrine and cortisol. As well as tobacco-specific carcinogen NNK (4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone), they can induce expressive DNA damage contributing to the cancer development. However, it is unknown whether stress hormones have genotoxic effects in oral keratinocytes. This study investigated the effects of stress hormones on DNA damage in a human oral keratinocyte cell line (NOK-SI). NOK-SI cells stimulated with norepinephrine or cortisol showed higher DNA damage compared to untreated cells. Norepinephrine-induced DNA damage was reversed by pre-treatment with beta-adrenergic blocker propranolol. Cells treated with NNK combined to norepinephrine displayed reduced levels of caspases 3 and 7. Cortisol also reduced the activity of pro-apoptotic enzymes. NNK or norepinephrine promoted single-strand breaks and alkali-label side breaks in the DNA of NOK-SI cells. Pre-treatment of cells with propranolol abolished these effects. Carcinogen NNK in the presence or absence of cortisol also induced DNA damage of these cells. The genotoxic effects of cortisol alone and hormone combined with NNK were blocked partially and totally, respectively, by the glucocorticoid receptor antagonist RU486. DNA damage promoted by NNK or cortisol and carcinogen combined to the hormone led to intracellular γH2AX accumulation. The effects caused by NNK and cortisol were reversed by propranolol and glucocorticoid receptor antagonist RU486, respectively. Propranolol inhibited the oxidation of basis induced by NNK in the presence of DNA-formamidopyrimidine glycosylase. DNA breaks induced by norepinephrine in the presence or absence of NNK resulted in higher 8OHdG cellular levels. This effect was also induced through beta-adrenergic receptors. Together, these findings indicate that stress hormones induce DNA damage of oral keratinocytes and could contribute to oral carcinogenesis.

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“…In the present study, all three pathways were more activated in NNK plus LPS-induced lung tumors as compared to the level in NNK-induced lung tumors, which was in line with the higher lung tumor size and multiplicity in NNK plus LPS-induced lung tumors. Both NNK and LPS, individually, are known to positively regulate Akt, NF-κB and STAT3 activation 4,5,,8–10,13,27,31 and therefore the dramatic activation of these proteins in NNK plus LPS-induced lung tumors could be due to additive/synergistic effects of the agents. Activation of the PI3K/Akt signaling pathway is negatively regulated by the tumor suppressor protein PTEN, which, in the preset study, was markedly down-regulated in NNK plus LPS-induced lung tumors, which may have contributed to increased activation of Akt, a well-established positive regulator of the NF-κB pathway.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide Enhances Mouse Lung Tumorigenesis

et al. 2013

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The association between pulmonary inflammation and lung cancer is well-established. However, currently there are no appropriate models that recapitulate inflammation-related lung cancer in humans. In the present study, we examined, in two tumor bioassays, enhancement by bacterial lipopolysaccharide (LPS) of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice. Mice that were treated with NNK alone developed 29.6 ± 9.8 and 36.2 ± 4.1 lung tumors/mouse in experiment 1 and 2, respectively. Chronic intranasal instillation of LPS to NNK-treated mice increased the multiplicity of lung tumors to 47.3 ± 16.1 and 51.2 ± 4.8 lung tumors/mouse in experiment 1 and 2, corresponding to a significant increase by 60% and 41%, respectively. Moreover, administration of LPS to NNK-pretreated mice significantly increased the multiplicity of larger tumors and histopathologically more advanced lesions (adenoma with dysplasia and adenocarcinoma), macrophage recruitment to the peritumoral area and expression of inflammation-, cell proliferation- and survival-related proteins. Overall, our findings demonstrated the promise of the NNK-LPS-A/J mice model to better understand inflammation-driven lung cancer, dissect the molecular pathways involved and identify more effective preventive and therapeutic agents against lung cancer.

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Effects of tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) on the activation of ERK1/2 MAP kinases and the proliferation of human mammary epithelial cells

Cited by 19 publications

References 32 publications

Water-pipe smoking promotes epithelial–mesenchymal transition and invasion of human breast cancer cells via ERK1/ERK2 pathways

Water-pipe smoking promotes epithelial–mesenchymal transition and invasion of human breast cancer cells via ERK1/ERK2 pathways

Stress hormones promote DNA damage in human oral keratinocytes

Lipopolysaccharide Enhances Mouse Lung Tumorigenesis

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