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

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.

Zhu J ，Jiang Y ，Yang X ，Wang S ，Xie C ，Li X ，Li Y ，Chen Y ，Wang X ，Meng Y ，Zhu M ，Wu R ，Huang C ，Ma X ，Geng S ，Wu J ，Zhong C ... -  《-》

(-)-Epigallocatechin-3-Gallate Inhibits Colorectal Cancer Stem Cells by Suppressing Wnt/β-Catenin Pathway.

Chen Y ，Wang XQ ，Zhang Q ，Zhu JY ，Li Y ，Xie CF ，Li XT ，Wu JS ，Geng SS ，Zhong CY ，Han HY ... -  《Nutrients》

Sonic hedgehog and Wnt/β-catenin pathways mediate curcumin inhibition of breast cancer stem cells.

Li X ，Wang X ，Xie C ，Zhu J ，Meng Y ，Chen Y ，Li Y ，Jiang Y ，Yang X ，Wang S ，Chen J ，Zhang Q ，Geng S ，Wu J ，Zhong C ，Zhao Y ... -  《-》

miR-19 targeting of GSK3β mediates sulforaphane suppression of lung cancer stem cells.

Cancer stem cells (CSCs) play a central role in the development of cancer. The canonical Wnt/β-catenin pathway is critical for maintaining stemness of CSCs. Phytochemicals from dietary compounds possess anti-CSCs properties and have been characterized as promising therapeutic agents for the prevention and treatment of many cancers. To date, the involvement and function of miR-19, a key oncogenic miRNA, in regulating Wnt/β-catenin pathway and lung CSCs has not been defined. Meanwhile, the effect of sulforaphane (SFN) on lung CSCs also remains to be elucidated. Here, we reported that lung CSCs up-regulated miR-19a and miR-19b expression. Overexpression of miR-19a/19b enhanced the ability of tumorsphere formation, up-regulated the expression of lung CSCs markers, increased Wnt/β-catenin pathway activation and β-catenin/TCF transcriptional activity in lung CSCs. In contrary, down-regulation of miR-19 suppressed lung CSCs activity and Wnt/β-catenin activation. We further revealed that miR-19 activated Wnt/β-catenin pathway by directly targeting GSK3β, the key negative modulator of this pathway. Moreover, we showed that SFN exhibited inhibitory effect on lung CSCs through suppressing miR-19 and Wnt/β-catenin pathway. Taken together, these data illustrate the role of miR-19 in regulating lung CSCs traits and miR-19/GSK3β/β-catenin axis in SFN intervention of lung CSCs. Findings from this study could provide important new insights into the molecular mechanisms of lung CSCs regulation as well as its target intervention.

Zhu J ，Wang S ，Chen Y ，Li X ，Jiang Y ，Yang X ，Li Y ，Wang X ，Meng Y ，Zhu M ，Ma X ，Huang C ，Wu R ，Xie C ，Geng S ，Wu J ，Zhong C ，Han H ... -  《-》

Inhibition of green tea polyphenol EGCG((-)-epigallocatechin-3-gallate) on the proliferation of gastric cancer cells by suppressing canonical wnt/β-catenin signalling pathway.

Yang C ，Du W ，Yang D 《-》