Chemotherapy: Open Access
Open Access
ISSN: 2167-7700
ISSN: 2167-7700
Department of Chemistry, Xinzhou Teachers University, Xinzhou, Shanxi 034000, China
Research Article
Discovery of Novel Hybrid with Resveratrol and Hantzsch Ester Derivatives as Activators Induce Autophagic Cell Death in Tumoral NCI-H460 Cells through Production of ROS
Author(s): Yu-Ting Du*, Hong-Liang Wang, San-Hu Zhao and Xiao-Juan Zhang
Based on the integrated fragment-based drug design, synthesis, and in vivo evaluations, a series of novel resveratrol and hantzsch ester (ReHa) derivatives are discovered as autophagic death inducer. Compound ReHa-2 is the most potent inducer with IC50 values as low as 9.9 mM compare with the molecule Nitrendipine (NIP) in autophagic cell death. Compound ReHa-2 lead to autophagic cells death instead of necrosis or apoptosis in human NCI-H460 cells. Mechanistic study uncovers that ReHa-2 is capable of increasing protein LC3-II (a marker of autophagy) and reducing p62 in a time and dose-dependent manner. Furthermore, ReHa-2 can activate MAPKs and Akt signal pathway. In addition, we identified that ReHa-2 triggered more ROS generation compare with NIP in NCI-H460 cells. Noticeably, the cytotoxicity induced by ReHa-2 against NCI-H460 cells can be significantly revised by pretreat.. View More»
DOI:
10.35248/2167-7700.22.10.161