2-(4-methoxyphenylthio)-5,8-dimethoxy-1,4-naphthoquinone induces apoptosis via ROS-mediated MAPK and STAT3 signaling pathway in human gastric cancer cells
| Autor: | Jia-Ru Wang, Hui Xue, Xian-Ji Piao, Cheng-Hao Jin, Tong Zhang, Shi-Nong Wang, Wan-Ting Xu, Jin-Qian Li, Yu Zhang, Gui-Nan Shen, Long-Kui Cao, Hao Wang, Ying-Hua Luo, Yi Zhang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway STAT3 Transcription Factor Cell Survival p38 mitogen-activated protein kinases 030106 microbiology Apoptosis Stat3 Signaling Pathway 03 medical and health sciences 0302 clinical medicine Stomach Neoplasms Cell Line Tumor Humans Pharmacology (medical) Protein kinase A Cell Proliferation Pharmacology Kinase Chemistry Infectious Diseases Oncology 030220 oncology & carcinogenesis Cancer cell Cancer research Apoptotic signaling pathway Mitogen-Activated Protein Kinases Reactive Oxygen Species Naphthoquinones Signal Transduction |
| Zdroj: | Journal of chemotherapy (Florence, Italy). 31(4) |
| ISSN: | 1973-9478 |
| Popis: | The 1,4-naphthoquinones and their derivatives have garnered great interest due to their antitumor pharmacological properties in various cancers; however, their clinical application is limited by side effects. In this study, to reduce side effects and improve therapeutic efficacy, a novel 1,4-naphthoquinone derivative-2-(4-methoxyphenylthio)-5,8-dimethoxy-1,4-naphthoquinone (MPTDMNQ) was synthesized. We investigated the effects and underlying mechanisms of MPTDMNQ on cell viability, apoptosis, and reactive oxygen species (ROS) generation in human gastric cancer cells. Our results showed that MPTDMNQ decreased cell viability in nine human gastric cancer cell lines. MPTDMNQ significantly induced apoptosis accompanied by the accumulation of ROS in GC cells. However, pre-treatment with the ROS scavenger N-acetyl-L-cysteine (NAC) attenuated the MPTDMNQ-induced apoptosis. Moreover, MPTDMNQ decreased the phosphorylation levels of extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 (STAT3); and increased the phosphorylation levels of c-Jun N-terminal kinase (JNK) and p38 kinase. However, phosphorylation was inhibited by NAC and a mitogen-activated protein kinase (MAPK) inhibitor. These findings showed that MPTDMNQ induced AGS cell apoptosis via ROS-mediated MAPK and STAT3 signaling pathways. Thus, MPTDMNQ may be a promising candidate for treating gastric cancer. |
| Databáze: | OpenAIRE |
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