Novel Piperlongumine Derivative C12 Induces Cell Cycle Arrest, Apoptosis, and Autophagy in A549 Cells
LONG Haitao1, LEI Xue1, CHEN Jiayi1, MENG Jiao2, SHAO Lihui2, LI Zhurui1,3, CHEN Danping1, WANG Zhenchao1,2,3, ZHOU Yue1,3*, LI Chengpeng1,3*
This study aimed to investigate the inhibitory effect of Piperlongumine derivative C12 on NSCLC (non-small cell lung cancer) cell line A549 and its mechanism in vitro. MTT assay and colony formation assay were used to detect the effect of C12 on cell proliferation. Scratch assay and Transwell assay were used to detect the effects of C12 on cell migration and invasion. Cell cycle and apoptosis were detected by flow cytometry. Transcriptome sequencing was used to predict DEGs (differentially expressed genes) after C12 treatment. Western blot was used to verify the effect of C12 on the expression of related proteins. The results showed that C12 could effectively inhibit the proliferation, migration, and invasion of A549 cells, arrest cell cycle at G2/M phase and induce cell apoptosis by regulating the expression of Bax and Bcl-2. The regulatory genes were mainly present in the chromosomal component and were significantly enriched in molecular functions related to catalytic activity and DNA binding, cell cycle biological processes, and MAPK and PI3K/Akt signaling pathways. C12 could increase intracellular ROS level and activate MAPK signaling pathway to induce cell apoptosis by up-regulating the expression of p-JNK, p-Erk1/2 and p-p38. At the same time, C12 induced autophagy by down-regulating p-Akt and p-mTOR and up-regulating LC3-II. In conclusion, C12 could activate MAPK signaling pathway to induce apoptosis and inhibit PI3K/Akt/m-TOR signaling pathway to induce autophagy in A549 cells.
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