Propolin C Inhibited Migration and Invasion via Suppression of EGFR-Mediated Epithelial-to-Mesenchymal Transition in Human Lung Cancer Cells.

Jih-Tung Pai,Yann-Lii Leu,Yi-Chin Lee,Si-Ying Chen,Meng-Shih Weng

doi:10.1155/2018/7202548

Abstract

Controlling lung cancer cell migration and invasion via epithelial-to-mesenchymal transition (EMT) through the regulation of epidermal growth factor receptor (EGFR) signaling pathway has been demonstrated. Searching biological active phytochemicals to repress EGFR-regulated EMT might prevent lung cancer progression. Propolis has been used as folk medicine in many countries and possesses anti-inflammatory, antioxidant, and anticancer activities. In this study, the antimigration and anti-invasion activities of propolin C, a c-prenylflavanone from Taiwanese propolis, were investigated on EGFR-regulated EMT signaling pathway. Cell migration and invasion activities were dose-dependently suppressed by noncytotoxic concentration of propolin C. Downregulations of vimentin and snail as well as upregulation of E-cadherin expressions were through the inhibition of EGFR-mediated phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinase (ERK) signaling pathway in propolin C-treated cells. In addition, EGF-induced migration and invasion were suppressed by propolin C-treated A549 lung cancer cells. No significant differences in E-cadherin expression were observed in EGF-stimulated cells. Interestingly, EGF-induced expressions of vimentin, snail, and slug were suppressed through the inhibition of PI3K/Akt and ERK signaling pathway in propolin C-treated cells. Inhibition of cell migration and invasion by propolin C was through the inhibition of EGF/EGFR-mediated signaling pathway, followed by EMT suppression in lung cancer.

Highlights

Propolis is a resinous material collected from buds and exudates of plants to build and defend the hive by honeybee
To evaluate the antiproliferative activity of propolin C on epidermal growth factor receptor (EGFR)-mutated lung cancer cells, HCC827 cells were incubated with serial dosages of propolin C for 24 h and cell viability was detected
The results revealed that inhibition of migration and invasion by propolin C was through downregulation of EGFR/PI3K/Akt and extracellular signal-regulated kinase (ERK)-mediated Epithelial-to-mesenchymal transition (EMT) signaling pathways in EGFR-mutated HCC827 lung cancer cells

Summary

Introduction

Propolis is a resinous material collected from buds and exudates of plants to build and defend the hive by honeybee. Numerous studies have indicated the biological activities of propolis, such as antimicrobial, antiviral, anti-inflammatory, antioxidant, and antitumor activities [1,2,3,4]. According to plant origins and chemical compositions, propolis can be divided into six categories in the world [5]. Eight prenylflavanones of Taiwanese propolis, propolin A to H, have been identified and originate from the surface resinous materials of Macaranga tanarius L. fruits [12, 13]. The anticancer activities of propolins have been characterized in lung cancer, melanoma, and glioma cell models [14,15,16,17,18]; the anti-invasion and antimigration activities of these components are still unclear

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Conclusion