1. Academic Validation
  2. Novel 1,4-naphthoquinone derivatives induce apoptosis via ROS-mediated p38/MAPK, Akt and STAT3 signaling in human hepatoma Hep3B cells

Novel 1,4-naphthoquinone derivatives induce apoptosis via ROS-mediated p38/MAPK, Akt and STAT3 signaling in human hepatoma Hep3B cells

  • Int J Biochem Cell Biol. 2018 Mar;96:9-19. doi: 10.1016/j.biocel.2018.01.004.
Chang Liu 1 Gui-Nan Shen 1 Ying-Hua Luo 2 Xian-Ji Piao 3 Xue-Yuan Jiang 1 Ling-Qi Meng 1 Yue Wang 1 Yi Zhang 1 Jia-Ru Wang 1 Hao Wang 1 Wan-Ting Xu 1 Jin-Qian Li 1 Yang Liu 1 Yi-Qin Wu 1 Hu-Nan Sun 1 Ying-Hao Han 1 Mei-Hua Jin 1 Yu-Dong Cui 1 Nan-Zhu Fang 4 Cheng-Hao Jin 5
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Xinyang Road 2, 163319, Daqing, China.
  • 2 Department of Animal Science, College of Animal Science & Veterinary Medicine, Heilongjiang Bayi Agricultural University, Xinyang Road 2, 163319, Daqing, China.
  • 3 Department of Gynaecology and Obstetrics, The Fifth Affiliated Hospital of Harbin Medical University, Jianshe Road 213, 163316, Daqing, China.
  • 4 Department of Animal Science, College of Agriculture, Yanbian University, Gongyuan Street 997, 133002, Yanji, China. Electronic address: nzfang@ybu.edu.cn.
  • 5 Department of Biochemistry and Molecular Biology, College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Xinyang Road 2, 163319, Daqing, China. Electronic address: jinchenghao3727@qq.com.
Abstract

1,4-Naphthoquinone and its derivatives have shown some efficacy as therapeutic compounds for Cancer and inflammation, though their clinical application is limited by their side-effects. To reduce the toxicity of these compounds and optimize their effects, we synthesized two 1,4-naphthoquinone derivatives-2-butylsulfinyl- 1,4-naphthoquinone (BSNQ) and 2-octylsulfinyl-1,4-naphthoquinone (OSNQ)-and investigated their effects and underlying mechanisms in hepatocellular carcinoma cells. BSNQ and OSNQ decreased cell viability and significantly induced Apoptosis, accompanied by the accumulation of Reactive Oxygen Species (ROS). However, pretreatment with N-acetyl-l-cysteine, a specific ROS scavenger, blocked Apoptosis. Western blot results indicated that BSNQ and OSNQ up-regulated the phosphorylation of p38 and JNK, and down-regulated the phosphorylation of ERK, Akt and STAT3, and that these effects were blocked by N-acetyl-l-cysteine. Furthermore, BSNQ and OSNQ suppressed tumor growth and modulated MAPK and STAT3 signaling in mouse xenografts without detectable effects on body weight or hematological parameters. These results indicate that BSNQ and OSNQ induce Apoptosis in human hepatoma Hep3B cells via ROS-mediated p38/MAPK, Akt and STAT3 signaling pathways, suggesting that these 1,4-naphthoquinone derivatives may provide promising new Anticancer agents to treat HCC.

Keywords

1,4-Naphthoquinone derivatives; Apoptosis; Human hepatoma cells; ROS; Signaling pathways.

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