2. Academic Validation
  3. Discovery of the theobromine derivative MQS-14 that induces death of MGC-803 cells mainly through ROS-mediated mechanisms

Discovery of the theobromine derivative MQS-14 that induces death of MGC-803 cells mainly through ROS-mediated mechanisms

  • Eur J Med Chem. 2019 Jul 15:174:76-86. doi: 10.1016/j.ejmech.2019.04.044.
Ting Ma 1,  Qi-Sheng Ma 1,  Bin Yu 2,  Hong-Min Liu 3
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China.
  • 2 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210023, Jiangsu, China. Electronic address: zzuyubin@hotmail.com.
  • 3 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China. Electronic address: liuhm@zzu.edu.cn.
PMID: 31029946 DOI: 10.1016/j.ejmech.2019.04.044
Abstract

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.

Keywords

Apoptosis; DNA damage; Gastric cancer; MAPK pathway; Reactive oxygen species (ROS); Theobromine.

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