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.

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.

• Authors: Qing Shi, Zhou Jiang, Jingyi Yang, Yunlong Cheng, Yaqiong Pang, Ning Zheng, Jiahang Chen, Wenge Chen, Lee Jia
• Journal: The AAPS journal (AAPS J) Vol. 19 Issue 6 Pg. 1779-1790 (11 2017) ISSN: 1550-7416 [Electronic] United States
• PMID: 28842850 (Publication Type: Journal Article)

Chemical References

• Anticarcinogenic Agents
• Flavonoids
• Glycosides
• NF-kappa B
• STAT3 Transcription Factor
• STAT3 protein, human
• Cyclooxygenase 2
• PTGS2 protein, human
• ErbB Receptors

Topics

• Anticarcinogenic Agents (pharmacology)
• Cell Adhesion (drug effects)
• Cell Line, Tumor
• Cyclooxygenase 2 (physiology)
• ErbB Receptors (physiology)
• Flavonoids (pharmacology)
• Glycosides (pharmacology)
• Humans
• Medicine, Chinese Traditional
• Murraya (chemistry)
• NF-kappa B (physiology)
• Neoplasm Metastasis (prevention & control)
• STAT3 Transcription Factor (physiology)
• Signal Transduction (physiology)