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The chalcone 2′‐hydroxy‐4′,5′‐dimethoxychalcone activates death receptor 5 pathway and leads to apoptosis in human nonsmall cell lung cancer cells
Author(s) -
Yang Lina,
Su Ling,
Cao Congmei,
Xu Linyan,
Zhong Diansheng,
Xu Lijia,
Liu Xiangguo
Publication year - 2013
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.1161
Subject(s) - apoptosis , chop , downregulation and upregulation , cancer research , atf4 , reactive oxygen species , cancer cell , cancer , lung cancer , signal transduction , biology , programmed cell death , cell growth , chalcone , chemistry , microbiology and biotechnology , medicine , biochemistry , genetics , gene , stereochemistry
Natural chalcones have been proved to inhibit cancer cells with therapeutic potential, but the underlying molecular mechanism is still largely unexplored. Here, we identified a novel chalcone, 2′‐hydroxy‐4′,5′‐dimethoxychalcone (HDMC) and demonstrated that HDMC induced apoptosis in various nonsmall cell lung cancer cells. Further study showed that HDMC elevated cellular reactive oxygen species (ROS) levels, thus inducing expressions of ATF4 and C/EBP homologous protein (CHOP). Then, death receptor 5 (DR5) was upregulated through ATF4–CHOP axis and eventually resulted in apoptosis. We also found that downregulation of c‐FLIP L contributed to HDMC‐induced apoptosis. In conclusion, HDMC induces apoptosis in human nonsmall cell lung cancer cells via activation of DR5 signaling pathway, and ROS‐mediated ATF4–CHOP axis is involved in the process. Our results further supported the potential for HDMC to be developed as a new antitumor agent for cancer therapy or chemoprevention. © 2013 IUBMB Life, 65(6):533–543, 2013