Dual targeting of NUAK1 and ULK1 using the multitargeted inhibitor MRT68921 exerts potent antitumor activities

摘要

Expression levels of NUAK1 were screened in the Broad Institute Cancer Cell Line Encyclopedia (CCLE). NUAK1 expression levels were analyzed by western blot in 12 cancer cell lines and 2 normal cell lines. A549, NCI-H460, MNK45, and U251 cells were treated with 20 μM NUAK1 inhibitor WZ4003 for 0, 4, 8, and 12 h and analyzed by western blot. WZ4003 treatment induces phosphorylation of ULK1 and puncta of LC3 together with downregulation of p62 and upregulation of phosphorylated ATG13. Phosphorylation of NUAK1 downstream target MYPT1 is downregulated by WZ4003. Phosphorylated ULK1 protein levels (normalized to total ULK1), phosphorylated ATG13 protein levels (normalized to total ATG13), phosphorylated MYPT1 protein levels (normalized to total MYPT1), p62 protein levels (normalized to GAPDH), and LC3B protein levels (normalized to GAPDH),  = 3. Representative images of LC3B fluorescence in U251 cells and A549 cells treated with 20 μM WZ4003 for 0–12 h.