New naphthalene derivatives induce human lung cancer A549 cell apoptosis via ROS-mediated MAPKs, Akt, and STAT3 signaling pathways
Autor: | Yu Zhang, Gui-Nan Shen, Cheng-Hao Jin, Yu-Chao Feng, Hao Wang, Ying-Hua Luo, Tong Zhang, Chang-Yuan Wang, Yi Zhang, Jin-Qian Li, Wan-Ting Xu, Shi-Nong Wang, Jia-Ru Wang, Xian-Ji Piao |
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Rok vydání: | 2019 |
Předmět: |
STAT3 Transcription Factor
0301 basic medicine MAPK/ERK pathway Antineoplastic Agents Apoptosis Naphthalenes Toxicology Structure-Activity Relationship 03 medical and health sciences 0302 clinical medicine Tumor Cells Cultured Humans MTT assay Protein kinase A Protein kinase B Cell Proliferation chemistry.chemical_classification A549 cell Reactive oxygen species Dose-Response Relationship Drug Molecular Structure Kinase Chemistry General Medicine 030104 developmental biology A549 Cells 030220 oncology & carcinogenesis Cancer research Drug Screening Assays Antitumor Mitogen-Activated Protein Kinases Reactive Oxygen Species Proto-Oncogene Proteins c-akt Signal Transduction |
Zdroj: | Chemico-Biological Interactions. 304:148-157 |
ISSN: | 0009-2797 |
Popis: | 1,4-Naphthoquinone compounds are a class of organic compounds derived from naphthalene. They exert a wide variety of biological effects, but when used as anticancer drugs, have varying levels of side effects. In the present study, in order to reduce toxicity and improve the antitumor activity, we synthesized two novel 1,4-naphthoquinone derivatives, 2-(butane-1-sulfinyl)-1,4-naphthoquinone (BSQ) and 2-(octane-1-sulfinyl)-1,4-naphthoquinone (OSQ). We investigated the antitumor effects of BSQ and OSQ in human lung cancer cells and the underlying molecular mechanisms of these effects, focusing on the relationship between these compounds and reactive oxygen species (ROS) production. MTT assay and trypan blue exclusion assay results showed that BSQ and OSQ had significant cytotoxic effects in human lung cancer cells. Flow cytometry results indicated that the number of apoptotic cells and the intracellular ROS levels significantly increased after treatment with BSQ and OSQ. However, cell apoptosis was inhibited by pretreatment with the ROS scavenger N-acetyl- l -cysteine (NAC). Western blotting results showed that BSQ and OSQ increased the expression levels of p-p38 kinase and p-c-Jun N-terminal kinase (p-JNK), and decreased the expression levels of p-extracellular signal-regulated kinase (p-ERK), p-protein kinase B (p-Akt), and p-signal transducer and activator of transcription-3 (p-STAT3). These phenomena were blocked by mitogen-activated protein kinase (MAPK) inhibitors, Akt inhibitors and NAC. In conclusion, BSQ and OSQ induce human lung cancer A549 cell apoptosis by ROS-mediated MAPKs, Akt, and STAT3 signaling pathways. Therefore, BSQ and OSQ may be therapeutic potential agents for the treatment of human lung cancer. |
Databáze: | OpenAIRE |
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