Nuciferine, extracted from Nelumbo nucifera Gaertn, inhibits tumor-promoting effect of nicotine involving Wnt/β-catenin signaling in non-small cell lung cancer

Liu, Wei; Yi, Dandan; Guo, Jing; Xiang, Zhu-Xing; Deng, Linfeng; He, Lei

doi:10.1016/j.jep.2015.02.015

Cited by 81 publications

(52 citation statements)

References 46 publications

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“…Previous studies showed that nicotine can promote proliferation and invasion in several cancers via the Wnt/β-catenin pathway (9,13). In this study, we examined if the activation of Wnt/β-catenin and Wnt/PCP pathways by nicotine involved α7 nAChR in Cal27 cells.…”

Section: Resultsmentioning

confidence: 99%

“…The Wnt/β-catenin pathway has been also found to be connected to promote proliferation in non-small cell lung cancer after nicotine stimulation (6,9,10,13,34,35). We first found that nicotine can also activate the Wnt/β-catenin pathway in the TSCC cell line Cal27 in vitro .…”

Section: Discussionmentioning

confidence: 99%

“…Epithelial cells act as a mechanical barrier to reduce a portion of the nicotine and make it impossible to reach 10 mM in the tongue tissue. In many experiments about nicotine stimulation to lung tissue, various concentrations of nicotine have been used (6,7,9,10,13,14). They chose 1, 5, 0.08 or 6 µM to conduct subsequent functional experiments.…”

Section: Introductionmentioning

confidence: 99%

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Nicotine may promote tongue squamous cell carcinoma progression by activating the Wnt/β-catenin and Wnt/PCP signaling pathways

Wang

Jin

et al. 2017

Oncology Letters

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To investigate the effects and the possible underlying mechanisms of nicotine stimulation on tongue squamous cell carcinoma (TSCC) progression, a TSCC cell line Cal27 and 34 samples of paraffin-embedded TSCC were examined. Immunofluorescence, western blot analysis, and TOP/FOP flash, CCK-8, wound healing and Transwell invasion assays were used to evaluate Cal27 in response to nicotine stimulation. We also investigated expression levels of related proteins of Wnt/β-catenin and Wnt/PCP pathways in paraffin-embedded TSCC samples with or without a history of smoking by immunohistochemistry. Nicotine stimulation can promote proliferation, migration, and invasion of TSCC cells in vitro, downregulate E-cadherin, and activate the Wnt/β-catenin and Wnt/PCP pathways, which could be antagonized by the α7 nicotine acetylcholine receptor (α7 nAChR) inhibitor α-BTX. Moreover, the expression levels of β-catenin, Wnt5a and Ror2 were higher in TSCC patients with a history of smoking than those without a history of smoking. Our results suggest nicotine may promote tongue squamous carcinoma cells progression by activating the Wnt/β-catenin and Wnt/PCP signaling pathways and may play a significant role in the progression and metastasis of smoking-related TSCC.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nicotine may promote tongue squamous cell carcinoma progression by activating the Wnt/β-catenin and Wnt/PCP signaling pathways

Wang

Jin

et al. 2017

Oncology Letters

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“…As a pilot study, the anti-tumor activities and molecular mechanisms of nuciferine, an aporphine alkaloid extracted from lotus leaves, were selected for further study and validation in our investigation, on the basis of evidence from the literature and in vivo/in vitro experiments. For example, nuciferine has been reported in studies of melanoma [16] , non-small cell lung cancer [17] and the DU-145 cell line [18] . In addition, we predicted that nuciferine and melphalan would exhibit similar anti-tumor profiles against the tested tumor cell lines.…”

Section: Introductionmentioning

confidence: 99%

Identification of the anti-tumor activity and mechanisms of nuciferine through a network pharmacology approach

et al. 2016

Acta Pharmacol Sin

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Aim: Nuciferine is an aporphine alkaloid extracted from lotus leaves, which is a raw material in Chinese medicinal herb for weight loss. In this study we used a network pharmacology approach to identify the anti-tumor activity of nuciferine and the underlying mechanisms. Methods: The pharmacological activities and mechanisms of nuciferine were identified through target profile prediction, clustering analysis and functional enrichment analysis using our traditional Chinese medicine (TCM) network pharmacology platform. The antitumor activity of nuciferine was validated by in vitro and in vivo experiments. The anti-tumor mechanisms of nuciferine were predicted through network target analysis and verified by in vitro experiments. Results: The nuciferine target profile was enriched with signaling pathways and biological functions, including "regulation of lipase activity", "response to nicotine" and "regulation of cell proliferation". Target profile clustering results suggested that nuciferine to exert anti-tumor effect. In experimental validation, nuciferine (0.8 mg/mL) markedly inhibited the viability of human neuroblastoma SY5Y cells and mouse colorectal cancer CT26 cells in vitro, and nuciferine (0.05 mg/mL) significantly suppressed the invasion of 6 cancer cell lines in vitro. Intraperitoneal injection of nuciferine (9.5 mg/mL, ip, 3 times a week for 3 weeks) significantly decreased the weight of SY5Y and CT26 tumor xenografts in nude mice. Network target analysis and experimental validation in SY5Y and CT26 cells showed that the anti-tumor effect of nuciferine was mediated through inhibiting the PI3K-AKT signaling pathway and IL-1 levels in SY5Y and CT26 cells. Conclusion: By using a TCM network pharmacology method, nuciferine is identified as an anti-tumor agent against human neuroblastoma and mouse colorectal cancer in vitro and in vivo, through inhibiting the PI3K-AKT signaling pathways and IL-1 levels.

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“…Nuciferine [(R)-1,2-dimethoxyaporphine, PubChem CID: 10146] (▶ Fig. 1), an aromatic ring-containing alkaloid, has been shown to have beneficial pharmacological effects, such as dilating blood vessels [5], stimulating insulin secretion [6], ameliorating nonalcoholic fatty liver disease [7], and ameliorating atherosclerosis [8], as well as anti-HIV [9], antioxidant [10][11][12], anti-obesity [13], antihyperlipidemia [14], and antitumor effects [15,16]. Recently, we reported that lotus leaf extract significantly relaxed high K + -or ACh-contracted TRs [17].…”

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confidence: 99%

Nuciferine Relaxes Tracheal Rings via the Blockade of VDLCC and NSCC Channels

Yang

Lei

et al. 2017

Planta Med

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This study aimed to elucidate the mechanisms of nuciferine (a main aporphine alkaloid of lotus leaf extract), which can induce relaxation in contracted tracheal rings. Under Ca-free and 2 mM Ca conditions, we found that nuciferine had no effect on the resting muscle tone of tracheal rings. In contrast, nuciferine relaxed high K-contracted mouse tracheal rings in a dose-dependent manner and inhibited both Ca influx and voltage-dependent L-type Ca channel currents induced by high K. Similarly, nuciferine also inhibited acetylcholine-induced contractions in mouse tracheal rings in a dose-dependent manner. Meanwhile, both acetylcholine-induced intracellular Ca influx and whole-cell currents of nonselective cation channels were blocked by nuciferine. Together, the results indicate that nuciferine-induced relaxation in tracheal rings mainly occurred due to the inhibition of extracellular Ca influx through the blockade of voltage-dependent L-type Ca channels and/or nonselective cation channels. These results suggest that nuciferine has a therapeutic effect on respiratory diseases associated with the aberrant contraction of airway smooth muscles and/or bronchospasm.

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Nuciferine, extracted from Nelumbo nucifera Gaertn, inhibits tumor-promoting effect of nicotine involving Wnt/β-catenin signaling in non-small cell lung cancer

Cited by 81 publications

References 46 publications

Nicotine may promote tongue squamous cell carcinoma progression by activating the Wnt/β-catenin and Wnt/PCP signaling pathways

Nicotine may promote tongue squamous cell carcinoma progression by activating the Wnt/β-catenin and Wnt/PCP signaling pathways

Identification of the anti-tumor activity and mechanisms of nuciferine through a network pharmacology approach

Nuciferine Relaxes Tracheal Rings via the Blockade of VDLCC and NSCC Channels

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