Esculetin inhibits the proliferation of human lung cancer cells by targeting epithelial-to-mesenchymal transition of the cells

Abstract

Lung cancer is characterized by high mortality and it is a serious threat to human health. At present, strategies used for treatment of lung cancer are not effective. Hence, there is need for new drugs that can effectively treat the metastatic stage of the cancer. The present study investigated the effect of esculetin on proliferation and epithelial-mesenchymal transition (EMT) of human lung cancer (A549) cells, and the underlying mechanism.Cell proliferation was assessed using MTT assay. Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting were employed for the determination of changes in the expression levels of vimentin, Snail and E-cadherin mRNAs. Cell invasion and migration were determined using Transwell assay. The results showed that esculetin significantly and time-and dose-dependently inhibited the proliferation of A549 cells (p < 0.05). It also significantly and dose-dependently reduced their invasive ability (p < 0.05). The levels of expression of vimentin and Snail mRNAs were significantly and dose-dependently down-regulated in esculetin-treated A549 cells, when compared with the control cells (p < 0.05). Esculetin treatment significantly and dose-dependently upregulated the expression of E-cadherin mRNA (p < 0.05).These results demonstrate that esculetin effectively inhibits the proliferation of A549 cells, and regulates EMT of the cells via the down-regulation of vimentin and Snail, and up-regulation of E-cadherin expressions.

Antitumor Effects of Esculetin, a Natural Coumarin Derivative, against Canine Mammary Gland Tumor Cells by Inducing Cell Cycle Arrest and Apoptosis

“…Esculetin, a coumarin derivative, reportedly has several biological and pharmacological activities, including antioxidant, anti-inflammatory, and antiedema effects [ 22 , 29 ]. Moreover, recent studies have reported the anticancer effects of esculetin against various human cancers, including lung cancer [ 30 , 31 ], colorectal cancer [ 27 , 32 , 33 ], gastric cancer [ 34 ], and leukemia [ 35 , 36 , 37 , 38 ]. In particular, it is noteworthy in the antitumor effect of esculetin in human breast cancer, the counterpart of canine mammary cancer.…”

Sufentanil inhibits the proliferation and epithelial mesenchymal transition of lung cancer cells through Wnt/beta-catenin signaling pathway

“…Accumulating evidence has demonstrated that the inhibition of EMT can relieve the progression of lung cancer. Li et al [ 31 ] showed that esculetin regulates EMT in A549 cells by downregulating the expression of vimentin and Snail and upregulating the expression of E-cadherin, eventually inhibiting cell growth. Wang et al [ 32 ] confirmed that the expression of E-cadherin was upregulated, and that of N-cadherin, vimentin, and fibronectin was downregulated after icotinib treatment.…”

miR-24-3p Regulates Epithelial–Mesenchymal Transition and the Malignant Phenotype of Pancreatic Adenocarcinoma by Regulating ASF1B Expression

“…EMT is the process of cellular transformation from the epithelial phenotype into the mesenchymal phenotype, which is involved in tumor invasion and metastasis (Hugo et al 2007 ; Li et al 2019 ). During EMT, cells lose epithelial cell polarity and E-cadherin expression level and cell junctions decrease, which is accompanied by an enhanced migration and invasion ability (Craene and Berx 2013 ).…”