http://orcid.org/0000-0003-4431-2623
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Abstract
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.
Acknowledgment
We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.
Authors’ contribution
Cheng-Hao Jin and Long-Kui Cao conceived and designed the study. Jia-Ru Wang and Ying-Hua Luo wrote the paper and performed some of the experiments. Xian-Ji Piao and Yi Zhang assessed the cytotoxic effects. Hao Wang and Jin-Qian Li performed the apoptotic analyses. Wan-Ting Xu and Yu Zhang performed the cell cycle analyses. Shi-Nong Wang and Tong Zhang performed the western blot analyses. Hui Xue performed the signaling analyses. All of the authors have read and approved the final version of the manuscript.
Disclosure statement
No potential conflict of interest was reported by the authors.
Additional information
Funding
Notes on contributors
Jia-Ru Wang
Jia-Ru Wang, Master, Department of Biochemistry and Molecular Biology, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, China. Work in biochemistry and molecular biology research.
Gui-Nan Shen
Gui-Nan Shen, Doctor, Department of Biochemistry and Molecular Biology, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, China. Work in drug synthesis design and structure-activity relationship.
Ying-Hua Luo
Ying-Hua Luo, Master, College of Animal Science & Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, 163319, China. Work in grass science research.
Xian-Ji Piao
Xian-Ji Piao, Doctor, Department of Gynaecology and Obstetrics, the Fifth Affiliated Hospital of Harbin Medical University, Daqing, 163316, China. Work in biochemistry and molecular biology research.
Yi Zhang
Yi Zhang, Master, Department of Biochemistry and Molecular Biology, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, China. Work in biochemistry and molecular biology research.
Hao Wang
Hao Wang, Master, Department of Biochemistry and Molecular Biology, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, China. Work in biochemistry and molecular biology research.
Jin-Qian Li
Jin-Qian Li, Master, Department of Biochemistry and Molecular Biology, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, China. Work in biochemistry and molecular biology research.
Wan-Ting Xu
Wan-Ting Xu, Master, Department of Biochemistry and Molecular Biology, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, China. Work in genetics research.
Yu Zhang
Yu Zhang, Undergraduate, Department of Biochemistry and Molecular Biology, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, China. Work in biological engineering research.
Shi-Nong Wang
Shi-Nong Wang, Undergraduate, Department of Biochemistry and Molecular Biology, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, China. Work in biological engineering research.
Tong Zhang
Tong Zhang, Undergraduate, Department of Biochemistry and Molecular Biology, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, China. Work in pharmaceutical engineering research.
Hui Xue
Hui Xue, Undergraduate, Department of Biochemistry and Molecular Biology, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, China. Work in biotechnology research
Long-Kui Cao
Long-Kui Cao, Doctor, College of Food Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, China, National Coarse Cereals Engineering Research Center, Daqing, Heilongjiang, China. Work in food science and technology research.
Cheng-Hao Jin
Cheng-Hao Jin, Doctor, Department of Biochemistry and Molecular Biology, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, China; College of Food Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319, China; National Coarse Cereals Engineering Research Center, Daqing, Heilongjiang, China. Work in biochemistry and molecular biology research.