Discovery of the theobromine derivative MQS-14 that induces death of MGC-803 cells mainly through ROS-mediated mechanisms
| Autor: | Qi-Sheng Ma, Hong-Min Liu, Ting Ma, Bin Yu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Programmed cell death
Cell division Cell Survival MAP Kinase Signaling System DNA damage Antineoplastic Agents Apoptosis 01 natural sciences Structure-Activity Relationship 03 medical and health sciences Cell Line Tumor Drug Discovery Humans Viability assay Cell Proliferation 030304 developmental biology Pharmacology chemistry.chemical_classification 0303 health sciences Reactive oxygen species Molecular Structure 010405 organic chemistry Cell growth Organic Chemistry General Medicine Mitochondria 0104 chemical sciences Cell biology chemistry Cancer cell Theobromine Reactive Oxygen Species Cell Division DNA Damage |
| Zdroj: | European Journal of Medicinal Chemistry. 174:76-86 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2019.04.044 |
| Popis: | Reactive oxygen species (ROS) play crucial roles in maintaining redox balance and regulating physiological processes, ROS levels in cancer cells are relatively higher than those in normal cells. Therefore, elevating cellular ROS levels may be a viable strategy for selective killing of cancer cells. In this work, we synthesized a series of new theobromine derivatives and evaluated their cytotoxicity against gastric cancer cells MGC-803, SGC-7901 and HGC-27. Particularly, MQS-14 potently inhibited cell growth of MGC-803, SGC-7901 and HGC-27 cells at low micromolar levels. Mechanistic studies showed that compound MQS-14 decreased cell viability of MGC-803 cells and inhibited cell division revealed by the CFDA and EdU staining assays. MQS-14 increased cellular ROS levels and activated the MAPK pathway accompanied by the decreased p-ERK and increased p-JNK expression. MQS-14 also induced DNA damage and apoptosis in MGC-803 cells. To conclude, MQS-14 induced cell death of MGC-803 cells partly through elevating cellular ROS levels. |
| Databáze: | OpenAIRE |
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