Open Access

Two novel 1,4‑naphthoquinone derivatives induce human gastric cancer cell apoptosis and cell cycle arrest by regulating reactive oxygen species‑mediated MAPK/Akt/STAT3 signaling pathways

  • Authors:
    • Hao Wang
    • Ying‑Hua Luo
    • Gui‑Nan Shen
    • Xian‑Ji Piao
    • Wan‑Ting Xu
    • Yi Zhang
    • Jia‑Ru Wang
    • Yu‑Chao Feng
    • Jin‑Qian Li
    • Yu Zhang
    • Tong Zhang
    • Shi‑Nong Wang
    • Hui Xue
    • Hong‑Xing Wang
    • Chang‑Yuan Wang
    • Cheng‑Hao Jin
  • View Affiliations

  • Published online on: July 15, 2019     https://doi.org/10.3892/mmr.2019.10500
  • Pages: 2571-2582
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

1,4‑Naphthoquinone derivatives have superior anticancer effects, but their use has been severely limited in clinical practice due to adverse side effects. To reduce the side effects and extend the anticancer effects of 1,4‑naphthoquinone derivatives, 2‑(butane‑1‑sulfinyl)‑1,4‑naphthoquinone (BQ) and 2‑(octane‑1‑sulfinyl)‑1,4‑naphthoquinone (OQ) were synthesized, and their anticancer activities were investigated. The anti‑proliferation effects, determined by MTT assays, showed that BQ and OQ significantly inhibited the viability of gastric cancer cells and had no significant cytotoxic effect on normal cell lines. The apoptotic effect was determined by flow cytometry, and the results showed that BQ and OQ induced cell apoptosis by regulating the mitochondrial pathway and cell cycle arrest at the G2/M phase via inhibition of the Akt signaling pathway in AGS cells. Furthermore, BQ and OQ significantly increased the levels of reactive oxygen species (ROS) and this effect was blocked by the ROS scavenger NAC in AGS cells. BQ and OQ induced apoptosis by upregulating the protein expression of p38 and JNK and downregulating the levels of ERK and STAT3. Furthermore, expression levels of these proteins were also blocked after NAC treatment. These results demonstrated that BQ and OQ induced apoptosis and cell cycle arrest at the G2/M phase in AGS cells by stimulating ROS generation, which caused subsequent activation of MAPK, Akt and STAT3 signaling pathways. Thus, BQ and OQ may serve as potential therapeutic agents for the treatment of human gastric cancer.
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September 2019
Volume 20 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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APA
Wang, H., Luo, Y., Shen, G., Piao, X., Xu, W., Zhang, Y. ... Jin, C. (2019). Two novel 1,4‑naphthoquinone derivatives induce human gastric cancer cell apoptosis and cell cycle arrest by regulating reactive oxygen species‑mediated MAPK/Akt/STAT3 signaling pathways. Molecular Medicine Reports, 20, 2571-2582. https://doi.org/10.3892/mmr.2019.10500
MLA
Wang, H., Luo, Y., Shen, G., Piao, X., Xu, W., Zhang, Y., Wang, J., Feng, Y., Li, J., Zhang, Y., Zhang, T., Wang, S., Xue, H., Wang, H., Wang, C., Jin, C."Two novel 1,4‑naphthoquinone derivatives induce human gastric cancer cell apoptosis and cell cycle arrest by regulating reactive oxygen species‑mediated MAPK/Akt/STAT3 signaling pathways". Molecular Medicine Reports 20.3 (2019): 2571-2582.
Chicago
Wang, H., Luo, Y., Shen, G., Piao, X., Xu, W., Zhang, Y., Wang, J., Feng, Y., Li, J., Zhang, Y., Zhang, T., Wang, S., Xue, H., Wang, H., Wang, C., Jin, C."Two novel 1,4‑naphthoquinone derivatives induce human gastric cancer cell apoptosis and cell cycle arrest by regulating reactive oxygen species‑mediated MAPK/Akt/STAT3 signaling pathways". Molecular Medicine Reports 20, no. 3 (2019): 2571-2582. https://doi.org/10.3892/mmr.2019.10500