Nuciferine, extracted from Nelumbo nucifera Gaertn, inhibits tumor-promoting effect of nicotine involving Wnt/β-catenin signaling in non-small cell lung cancer
| Autor: | Wei Liu, Lin-Feng Deng, Zhu-Xing Xiang, Dan-Dan Yi, Lei He, Jian-Li Guo |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Nicotine Aporphines Lung Neoplasms Nuciferine Cyclin D Mice Nude Apoptosis Nelumbo Flow cytometry chemistry.chemical_compound Western blot Carcinoma Non-Small-Cell Lung Cell Line Tumor Drug Discovery medicine Animals Humans Medicine Chinese Traditional Wnt Signaling Pathway Pharmacology Mice Inbred BALB C medicine.diagnostic_test biology Traditional medicine Wnt signaling pathway Plant Leaves chemistry biology.protein Cancer research Liver function Neoplasm Transplantation Drugs Chinese Herbal medicine.drug |
| Zdroj: | Journal of Ethnopharmacology. 165:83-93 |
| ISSN: | 0378-8741 |
| DOI: | 10.1016/j.jep.2015.02.015 |
| Popis: | Ethnopharmacological relevance The leaves of Nelumbo nucifera Gaertn are recorded in the earliest written documentation of traditional Chinese medicinal as “Ben Cao Gang Mu”, a medicinal herb for blood clotting, dysentery and dizziness. Recently, nuciferine (NF), one of N. nucifera Gaertn leaf extracts has been shown to possess several pharmacological properties, including anti-viral and anti-cancer. The aim of this study is to investigate the underlying molecular mechanism of the anti-cancer activity of NF in NSCLC progression induced by nicotine Materials and methods The effect of NF on proliferation of A549 (human lung adenocarcinoma epithelial cell line) pretreated with or without nicotine was detected by tumor cell proliferation assay. TOP-Flash reporter assay was applied to investigate the activity of Wnt/β-catenin signaling in tumor cells in the presence of NF and/or nicotine. Apoptosis was measured using a FITC-Annexin V and PI detection kit by flow cytometry. In addition, mRNA or protein expression levels were respectively tested by quantitative RT-PCR or western blot. In vivo experiments, tumor samples were fixed in formalin and embedded in paraffin for additional analyses by immunohistochemistry and TUNEL staining. Results NF significantly inhibited the proliferation of NSCLC cells in the presence of nicotine, suppressed the activity of Wnt/β-catenin signaling, enhanced the stabilization of Axin, and induced apoptosis. NF down-regulated the expression levels of β-catenin and its downstream targets including c-myc, cyclin D and VEGF-A. NF also decreased the ratio of Bcl-2/Bax, which may explain the pro-apoptosis effect of NF. In tumor xenograft nude mice, NF not only inhibited the growth of non-small cell lung cancer (NSCLC) cells, but also remarkably alleviated the injury induced by nicotine in liver function. Conclusions NF has the remarkable effect to inhibit nicotine-induced NSCLC progression, which was due to its ability to reduce the activity of Wnt/β-catenin signaling. Thus, the work stated here emphasizes the importance of this traditional medicine and presents a potential novel alternative to NSCLC prevention and therapy. |
| Databáze: | OpenAIRE |
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