Bergamottin Suppresses Metastasis of Lung Cancer Cells through Abrogation of Diverse Oncogenic Signaling Cascades and Epithelial-to-Mesenchymal Transition

Abstract

Bergamottin (BGM) is a naturally occurring furanocoumarin and is known to inhibit the growth of tumor cells. However, there is no available evidence that BGM has an inhibitory effect on cancer metastasis, specifically on the epithelial-to-mesenchymal transition (EMT) process in the malignant cells. Here we aimed to evaluate the antimetastatic potential of BGM in human lung adenocarcinoma cells. Our results demonstrate that BGM can block EMT, and observed inhibition was accompanied by downregulation of fibronectin, vimentin, N-cadherin, twist and snail expression, and upregulation of occludin and E-cadherin. Interestingly, transforming growth factor-beta (TGF-beta)-induced upregulation of fibronectin, vimentin, N-cadherin, twist and snail, and downregulation of occludin and E-cadherin, were abrogated by BGM treatment. Moreover, the treatment of BGM repressed TGF-beta-induced cell invasive potential. BGM treatment also inhibited multiple oncogenic cascades such as PI3K/Akt/mTOR. Overall, the results demonstrate the potential antimetastatic activity of BGM against lung cancer cells.