DMU-212 against EGFR-mutant non-small cell lung cancer via AMPK/PI3K/Erk signaling pathway

Xiao-Ping Zhao; Xiao-Li Zheng; Min Huang; Ya-Jia Xie; Xiao-Wen Nie; Ali Adnan Nasim; Xiao-Jun Yao; Xing-Xing Fan

doi:10.1016/j.heliyon.2023.e15812

DMU-212 against EGFR-mutant non-small cell lung cancer via AMPK/PI3K/Erk signaling pathway

Heliyon. 2023 Apr 26;9(5):e15812. doi: 10.1016/j.heliyon.2023.e15812. eCollection 2023 May.

Authors

Xiao-Ping Zhao¹, Xiao-Li Zheng¹, Min Huang¹, Ya-Jia Xie¹, Xiao-Wen Nie¹, Ali Adnan Nasim¹, Xiao-Jun Yao¹, Xing-Xing Fan¹

Affiliation

¹ Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Dr. Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, SAR, China.

Abstract

Although some important advances have been achieved in clinical and diagnosis in the past few years, the management of non-small cell lung cancer (NSCLC) is ultimately dissatisfactory due to the low overall cure and survival rates. Epidermal growth factor (EGFR) has been recognized as a carcinogenic driver and is a crucial pharmacological target for NSCLC. DMU-212, an analog of resveratrol, has been reported to have significant inhibitory effects on several types of cancer. However, the effect of DMU-212 on lung cancer remains unclear. Therefore, this study aims to determine the effects and underlying mechanism of DMU-212 on EGFR-mutant NSCLC cells. The data found that the cytotoxicity of DMU-212 on three EGFR-mutant NSCLC cell lines was significantly higher than that of normal lung epithelial cell. Further study showed that DMU-212 can regulate the expression of cell cycle-related proteins including p21 and cyclin B1 to induce G2/M phase arrest in both H1975 and PC9 cells. Moreover, treatment with DMU-212 significantly promoted the activation of AMPK and simultaneously down-regulated the expression of EGFR and the phosphorylation of PI3K, Akt and ERK. In conclusion, our study suggested that DMU-212 inhibited the growth of NSCLCs via targeting of AMPK and EGFR.

Keywords: DMU-212; EGFR mutation; EGFR-AMPK pathway; Lung cancer; NSCLC.