The chalcone 2′-hydroxy-4′,5′-dimethoxychalcone activates death receptor 5 pathway and leads to apoptosis in human nonsmall cell lung cancer cells
| Autor: | Ling Su, Xiangguo Liu, Lina Yang, Diansheng Zhong, Lijia Xu, Cong-Mei Cao, Linyan Xu |
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| Rok vydání: | 2013 |
| Předmět: |
Transcriptional Activation
Chalcone Lung Neoplasms Clinical Biochemistry CASP8 and FADD-Like Apoptosis Regulating Protein Gene Expression Apoptosis Biology CHOP Biochemistry chemistry.chemical_compound Chalcones Downregulation and upregulation Carcinoma Non-Small-Cell Lung Cell Line Tumor Genetics Humans Molecular Biology chemistry.chemical_classification Reactive oxygen species ATF4 Cell Cycle Checkpoints Cell Biology Endoplasmic Reticulum Stress Activating Transcription Factor 4 Antineoplastic Agents Phytogenic Up-Regulation Cell biology Receptors TNF-Related Apoptosis-Inducing Ligand chemistry Cancer cell Drug Screening Assays Antitumor Signal transduction Reactive Oxygen Species Transcription Factor CHOP Drugs Chinese Herbal Signal Transduction |
| Zdroj: | IUBMB Life. 65:533-543 |
| ISSN: | 1521-6543 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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