L. Su and L. Yang contributed equally to this work.
The chalcone 2′-hydroxy-4′,5′-dimethoxychalcone activates death receptor 5 pathway and leads to apoptosis in human nonsmall cell lung cancer cells†
Article first published online: 3 APR 2013
Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.
Volume 65, Issue 6, pages 533–543, June 2013
How to Cite
Yang, L., Su, L., Cao, C., Xu, L., Zhong, D., Xu, L. and Liu, X. (2013), The chalcone 2′-hydroxy-4′,5′-dimethoxychalcone activates death receptor 5 pathway and leads to apoptosis in human nonsmall cell lung cancer cells. IUBMB Life, 65: 533–543. doi: 10.1002/iub.1161
- Issue published online: 23 MAY 2013
- Article first published online: 3 APR 2013
- Manuscript Accepted: 6 FEB 2013
- Manuscript Revised: 5 FEB 2013
- Manuscript Received: 16 OCT 2012
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-FLIPL 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