Zerumbone attenuates TGF-β1-mediated epithelial–mesenchymal transition via upregulated E-cadherin expression and downregulated Smad2 signalling pathways in non-small cell lung cancer (A549) cells

Abstract

Zerumbone, a sesquiterpene compound of edible ginger (Zingiber zerumbet), has been tested for its anti-EMT and anti-metastatic properties in TGF-β1-stimulated human lung cancer (A549) cells. Zerumbone (10/20 µM) treatment prior to TGF-β1-stimulation reversed the adverse morphological changes (fibroblastic-to-epithelial phenotype) and up-regulated the E-cadherin expression against TGF-β1-induced down-regulation. Immunofluorescence and luciferase activity data confirmed the up-regulated E-cadherin expression and transcriptional activity by zerumbone under TGF-β1-stimulation. Further evidence showed that zerumbone decreased TGF-β1-mediated phosphorylation and transcriptional activity of Smad2, but not Smad3. These results revealed that zerumbone inhibits the TGF-β-induced EMT via up-regulation of E-cadherin and down-regulation of Smad2 signalling pathways. Findings from wound-healing, invasion and colony formation experiments proved that zerumbone inhibits TGF-β1-mediated (metastatic) migration, invasion and anchorage-independent growth. Besides, zerumbone alone is capable of inducing autophagy and apoptosis in A549 cells. These results conclude that anti-EMT and anti-metastatic activities of zerumbone may contribute to the development of food-based chemopreventive drugs for non-small cell lung cancer treatment.

Keywords

• Zerumbone
• EMT
• E-cadherin
• Smad2
• Metastasis
• Wound-healing