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The compound 2-benzylthio-5,8-dimethoxynaphthalene-1,4-dione leads to apoptotic cell death by increasing the cellular reactive oxygen species levels in Ras-mutated liver cancer cells.
Shen, Gui-Nan; Li, Jing; Jin, Ying-Hua; Sun, Hu-Nan; Hao, Ying-Ying; Jin, Mei-Hua; Liu, Ren; Li, Wei-Long; Zhang, Yong-Qing; Yu, Jia-Bin; Yu, Nan-Nan; Wang, Wei-Dong; Yu, Li-Yun; Kim, Ji-Su; Kwon, Taeho; Han, Ying-Hao.
Afiliación
  • Shen GN; College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China.
  • Li J; College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China.
  • Jin YH; Library and Information Center, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China.
  • Sun HN; College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China.
  • Hao YY; College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China.
  • Jin MH; College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China.
  • Liu R; College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China.
  • Li WL; College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China.
  • Zhang YQ; College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China.
  • Yu JB; College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China.
  • Yu NN; College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China.
  • Wang WD; College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China.
  • Yu LY; College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China.
  • Kim JS; Primate Resources Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, Jeonbuk 56216, Republic of Korea.
  • Kwon T; Primate Resources Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup-si, Jeonbuk 56216, Republic of Korea.
  • Han YH; College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China.
Exp Ther Med ; 20(5): 82, 2020 Nov.
Article en En | MEDLINE | ID: mdl-32968439
ABSTRACT
The aim of the present study was to verify the pro-apoptotic anticancer potential of several 5,8-dimethoxy-1,4-phthoquinone (DMNQ) derivatives in Ras-mediated tumorigenesis. MTT assays were used to detect cellular viability and flow cytometry was performed to assess intracellular reactive oxygen species (ROS) levels and apoptosis. The expression levels of proteins were detected via western blotting. Among the 12 newly synthesized DMNQ derivatives, 2-benzylthio-5,8-dimethoxynaphthalene-1,4-dione (BZNQ; component #1) significantly reduced cell viability both in mouse NIH3T3 embryonic fibroblasts cells (NC) and H-RasG12V transfected mouse NIH3T3 embryonic fibroblasts cells (NR). Moreover, BZNQ resulted in increased cytotoxic sensitivity in Ras-mutant transfected cells. Furthermore, the reactive oxygen species (ROS) levels in H-RasG12V transfected HepG2 liver cancer cells (HR) were significantly higher compared with the levels in HepG2 liver cancer cells (HC) following BZNQ treatment, which further resulted in increased cellular apoptosis. Eliminating cellular ROS using an ROS scavenger N-acetyl-L-cysteine markedly reversed BZNQ-induced cellular ROS accumulation and cell apoptosis in HC and HR cells. Western blotting results revealed that BZNQ significantly downregulated H-Ras protein expression and inhibited the Ras-mediated downstream signaling pathways such as protein kinase B, extracellular signal-related kinase and glycogen synthase kinase phosphorylation and ß-catenin protein expression. These results indicated that the novel DMNQ derivative BZNQ may be a therapeutic drug for Ras-mediated liver tumorigenesis. The results of the current study suggest that BZNQ exerts its effect by downregulating H-Ras protein expression and Ras-mediated signaling pathways.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: Exp Ther Med Año: 2020 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: Exp Ther Med Año: 2020 Tipo del documento: Article