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A Flavonoid Glycoside Compound from Murraya paniculata (L.) Interrupts Metastatic Characteristics of A549 Cells by Regulating STAT3/NF-κB/COX-2 and EGFR Signaling Pathways

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Abstract

Metastasis remains the leading cause of death from lung carcinoma. It is urgent to find safe and efficient pre-metastasis preventive agents for cancer survivors. We isolated a flavonoid glycoside, hexamethoxy flavanone-o-[rhamnopyranosyl-(1 → 4)-rhamnopyranoside (HMFRR), from the traditional Chinese medicine (TCM) Murraya paniculata (L.) that can effectively inhibit the adhesion, migration, and invasion of lung adenocarcinoma A549 cells in vitro. Molecular and cellular studies demonstrated that HMFRR significantly downregulated the expressions of cell adhesion-related and invasion-related molecules such as integrin β1, EGFR, COX-2, MMP-2, and MMP-9 proteins. Additionally, HMFRR effectively downregulated the expressions of epithelial–mesenchymal transition (EMT) markers (N-cadherin and vimentin) and upregulated that of E-cadherin. Moreover, these inhibitions were mediated by interrupting STAT3/NF-κB/COX-2 and EGFR/PI3K/AKT signaling pathways. Furthermore, HMFRR counteracted the expressions of cell adhesion molecules (ICAM-1, VCAM-1, and E-selectin) stimulated by interleukin-1β in human pulmonary microvascular endothelial cells (HPMECs). As a result, HMFRR interrupted the adhesion of A549 cells to HPMECs. Collectively, these results indicate that HMFRR may become a good candidate for cancer metastatic chemopreventive agents by interrupting the STAT3/NF-κB/COX-2 and EGFR signaling pathways.

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Acknowledgements

This research was supported by grants from National Natural Science Foundation of China (U1505225), Ministry of Science and Technology of China (MOST 2015CB931804) and Fujian Development and Reform Commission project no. 829054 (2014/168), and Education Ministry of Fujian Province of China (JA15057)

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Authors and Affiliations

  1. Cancer Metastasis Alert and Prevention Center, and Biopharmaceutical Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou University, Fuzhou, 350002, China

    Qing Shi, Zhou Jiang, Jingyi Yang, Yunlong Cheng, Yaqiong Pang, Ning Zheng, Jiahang Chen, Wenge Chen & Lee Jia

  2. Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China

    Zhou Jiang & Lee Jia

  3. Cancer Metastasis Alert and Prevention Center, Fuzhou University, Sunlight Building, 6FL; Science Park, Xueyuan Road, University Town, Fuzhou, Fujian, 350116, China

    Lee Jia

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  1. Qing Shi
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Electronic Supplementary Material

Figure S1

1H–NMR spectrum of HMFRR in DMSO. (JPEG 453 kb)

Figure S2

13C–NMR spectrum of HAM in DMSO. (JPEG 419 kb)

Figure S3

Effects of HMFRR on migration and invasion of A549 cells. (JPEG 607 kb)

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Shi, Q., Jiang, Z., Yang, J. et al. A Flavonoid Glycoside Compound from Murraya paniculata (L.) Interrupts Metastatic Characteristics of A549 Cells by Regulating STAT3/NF-κB/COX-2 and EGFR Signaling Pathways. AAPS J 19, 1779–1790 (2017). https://doi.org/10.1208/s12248-017-0134-0

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