Wnt/β-catenin pathway mediates (−)-Epigallocatechin-3-gallate (EGCG) inhibition of lung cancer stem cells

• Published in: Biochemical and biophysical research communications 2017-01, Vol.482 (1), p.15-21
• Main Authors: Zhu, Jianyun, Jiang, Ye, Yang, Xue, Wang, Shijia, Xie, Chunfeng, Li, Xiaoting, Li, Yuan, Chen, Yue, Wang, Xiaoqian, Meng, Yu, Zhu, Mingming, Wu, Rui, Huang, Cong, Ma, Xiao, Geng, Shanshan, Wu, Jieshu, Zhong, Caiyun
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; A549 Cells; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Catechin - analogs & derivatives; Catechin - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Dose-Response Relationship, Drug; EGCG; Humans; INHIBITION; Lung cancer stem cells; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; LUNGS; NEOPLASMS; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; STEM CELLS; Wnt Signaling Pathway - drug effects; Wnt/β-catenin pathway
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.11.038

Cancer stem cells (CSCs) play essential role in the progression of many tumors. Wnt/β-catenin pathway is crucial in maintaining the stemness of CSCs. (−)-Epigallocatechin-3-gallate (EGCG), the major bioactive component in green tea, has been shown to possess anti-cancer activity. To date, the interventional effect of EGCG on lung CSCs has not been elucidated yet. In the present study, tumorsphere formation assay was used to enrich lung CSCs from A549 and H1299 cells. We revealed that Wnt/β-catenin pathway was activated in lung CSCs, and downregulation of β-catenin, abolished lung CSCs traits. Our study further illustrated that EGCG effectively diminished lung CSCs activity by inhibiting tumorsphere formation, decreasing lung CSCs markers, suppressing proliferation and inducing apoptosis. Moreover, We showed that EGCG downregulated Wnt/β-catenin activation, while upregulation of Wnt/β-catenin dampened the inhibitory effects of EGCG on lung CSCs. Taken together, these results demonstrated the role of Wnt/β-catenin pathway in regulating lung CSCs traits and EGCG intervention of lung CSCs. Findings from this study could provide new insights into the molecular mechanisms of lung CSCs intervention. •EGCG inhibited lung CSCs activity.•EGCG inhibited lung CSCs activity via Wnt/β-catenin pathway suppression.•EGCG may prove to be a potential therapeutic agent for lung cancer.