Piperlongumine Induces Apoptosis and Pyroptosis of NCI-H460 Lung Cancer Cells Via Increasing ROS / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the inhibitory effect of different concentration of piperlongumine on the growth of lung cancer cells, and further study the effect of piperlongumine on the apoptosis and pyroptosis of NCI-H460 cancer cells by increasing ROS, and elucidate its new anti-tumor mechanism. METHODS: NCI-H460 lung cancer cells were cultured by conventional method, the control group and different concentration of piperlongumine treatment group were set up. MTT assay was used to evaluate the activity of NCI-H460 lung cancer cells, and cell colony assay was performed for the effect of colony formation of NCI-H460 cells. The NCI-H460 cells apoptosis and the growth inhibition of NCI-H460 cells via promotion of ROS levels were evaluated by flow cytometry, respectively. Western blotting was used to detect the expression of Bax, Bcl-2 and caspase-3 proteins after treated with piperlongumine. The effect of piperlongumine on the ROS-based NCI-H460 lung cells pyroptosis was confirmed by microscopic imaging. At the same time, the effect of ROS on apoptosis-related protein GSDME was detected by Western blotting. RESULTS: Piperlongumine inhibited lung cancer cells in a concentration dependent manner, with the IC50 value on NCI-H460 lung cancer of 13.1 μmol.L-1. Piperlongumine restrained the NCI-H460 colony formation in a concentration-dependent pattern and promoted NCI-H460 apoptosis. Piperlongumine promoted the expression of the pro-apoptotic proteins Bax and Cle-caspase-3, and inhibited the expression of the anti-apoptotic protein Bcl-2 in a concentration-dependent manner. Piperlongumine induced NCI-H460 cells apoptosis and pyroptosis by increasing intracellular ROS content, and ROS increased GSDME-N protein expression. CONCLUSION: Piperlongumine inhibits the growth of lung cancer cells, and induces apoptosis and pyroptosis of NCI-H460 cancer cells by promoting the levels of intracellular ROS.