The compound 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone induces apoptosis via reactive oxygen species-regulated mitogen-activated protein kinase, protein kinase B, and signal transducer and activator of transcription 3 signaling in human gast
Autor: | Cheng-Hao Jin, Jia-Ru Wang, Hao Wang, Long-Kui Cao, Mei-Hua Jin, Jin-Qian Li, Xian-Ji Piao, Ying-Hua Luo, Wan-Ting Xu, Hu-Nan Sun, Gui-Nan Shen, Meng Shen, Ying-Hao Han, Meng Lingqi, Yi Zhang, Yue Wang, Chang Liu, Yang Liu |
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Rok vydání: | 2018 |
Předmět: |
STAT3 Transcription Factor
0301 basic medicine MAPK/ERK pathway MAP Kinase Signaling System p38 mitogen-activated protein kinases Apoptosis 03 medical and health sciences 0302 clinical medicine Stomach Neoplasms Drug Discovery Humans STAT3 Protein kinase A Protein kinase B Cells Cultured biology Chemistry Kinase 1-Naphthylamine 030104 developmental biology 030220 oncology & carcinogenesis Mitogen-activated protein kinase Cancer cell Cancer research biology.protein Reactive Oxygen Species |
Zdroj: | Drug Development Research. 79:295-306 |
ISSN: | 0272-4391 |
Popis: | Hit, Lead & Candidate Discovery It is reported that 1,4-naphthoquinones and their derivatives have potent antitumor activity in various cancers, although their clinical application is limited by observed side effects. To improve the therapeutic efficacy of naphthoquinones in the treatment of cancer and to reduce side effects, we synthesized a novel naphthoquinone derivative, 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone (NTDMNQ). In this study, we explored the effects of NTDMNQ on apoptosis in gastric cancer cells with a focus on reactive oxygen species (ROS) production. Our results demonstrated that NTDMNQ exhibited the cytotoxic effects on gastric cancer cells in a dose-dependent manner. NTDMNQ significantly induced mitochondrial-related apoptosis in AGS cells and increased the accumulation of ROS. However, pre-treatment with N-acetyl-L-cysteine (NAC), an ROS scavenger, inhibited the NTDMNQ-induced apoptosis. In addition, NTDMNQ increased the phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK) and decreased the phosphorylation of extracellular signal-regulated kinase (ERK), protein kinase B (Akt), and Signal Transducer and Activator of Transcription 3 (STAT3); these effects were blocked by mitogen-activated protein kinase (MAPK) inhibitor and NAC. Taken together, the present findings indicate that NTDMNQ-induced gastric cancer cell apoptosis via ROS-mediated regulation of the MAPK, Akt, and STAT3 signaling pathways. Therefore, NTDMNQ may be a potential treatment for gastric cancer as well as other tumor types. |
Databáze: | OpenAIRE |
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