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  2. New naphthalene derivatives induce human lung cancer A549 cell apoptosis via ROS-mediated MAPKs, Akt, and STAT3 signaling pathways

New naphthalene derivatives induce human lung cancer A549 cell apoptosis via ROS-mediated MAPKs, Akt, and STAT3 signaling pathways

  • Chem Biol Interact. 2019 May 1;304:148-157. doi: 10.1016/j.cbi.2019.03.004.
Wan-Ting Xu 1 Gui-Nan Shen 1 Ying-Hua Luo 2 Xian-Ji Piao 3 Jia-Ru Wang 1 Hao Wang 1 Yi Zhang 1 Jin-Qian Li 1 Yu-Chao Feng 4 Yu Zhang 1 Tong Zhang 1 Shi-Nong Wang 1 Chang-Yuan Wang 5 Cheng-Hao Jin 6
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang, 163319, China.
  • 2 College of Animal Science & Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang, 163319, China.
  • 3 Department of Gynaecology and Obstetrics, The Fifth Affiliated Hospital of Harbin Medical University, Daqing, Heilongjiang, 163316, China.
  • 4 College of Food Science, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang, 163319, China.
  • 5 College of Food Science, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang, 163319, China. Electronic address: [email protected].
  • 6 Department of Biochemistry and Molecular Biology, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang, 163319, China; College of Food Science, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang, 163319, China. Electronic address: [email protected].
Abstract

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.

Keywords

1,4-Naphthoquinone derivatives; Apoptosis; Lung cancer cells; MAPKs; Reactive oxygen species; STAT3.

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