Daidzein induces apoptosis of non-small cell lung cancer cells by restoring STK4/YAP1 signaling

作者:Chen, Zhoumiao; Miao, Huiwen; Zhu, Ziyi; Zhang, Hu; Huang, Huixian*
来源:International Journal of Clinical and Experimental Medicine, 2017, 10(11): 15205-15212.

摘要

Aim: It was reported that daidzein (DAZ) exerted anti-cancer effects on many kinds of human cancer cells by inducing apoptosis. However, the molecular mechanisms are still vague and unclear. This study was designed to observe the inhibitory activity of DAZ on NSCLC cells and to further investigate possible mechanisms. Methods: Two NSCLC cell lines, namely A549 and H1299 were incubated with serially diluted DAZ solutions. The proliferation inhibition was assessed by MTT assay. The RNA interference technique was utilized to knockdown STK3 and STK4 respectively. Cell apoptosis was evaluated by TUNEL assay. Real-time PCR and western blotting were used to assess the expression levels of STK3, STK4, YAP1, phosphorylated YAP1 and cleaved caspase3. Results: DAZ incubation inhibited proliferation of NSCLC cells in a concentration-dependent manner by inducing apoptosis. Moreover, DAZ incubation significantly restored the expression of STK4 and further increased the phosphorylation of YAP1 which induced cell apoptosis, evidenced by elevated expression level of cleaved caspase3. However, the expression level of STK3 was unchanged by DAZ incubation. STK3 and STK4 were knocked-down by specific shRNAs. After DAZ incubation, silence of STK4 instead of STK3 impaired DAZ's apoptosis-inducing effects on NSCLC cells. Conclusions: DAZ inhibits NSCLC cells by inducing apoptosis by restoring STK4 expression and YAP1 phosphorylation.