PMID- 30592276
OWN - NLM
STAT- MEDLINE
DCOM- 20190524
LR  - 20200225
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 19
IP  - 3
DP  - 2019 Mar
TI  - Novel 1,4‑naphthoquinone derivatives induce reactive oxygen species‑mediated 
      apoptosis in liver cancer cells.
PG  - 1654-1664
LID - 10.3892/mmr.2018.9785 [doi]
AB  - Derivatives of 1,4‑naphthoquinone have excellent anti‑cancer effects, but their 
      use has been greatly limited due to their serious side effects. To develop 
      compounds with decreased side effects and improved anti‑cancer activity, two 
      novel types of 1,4‑naphthoquinone derivatives, 
      2,3‑dihydro‑2,3‑epoxy‑2‑propylsulfonyl‑5,8‑dimethoxy‑1,4‑naphthoquinone (EPDMNQ) 
      and 2,3‑dihydro‑2,3‑epoxy‑2‑nonylsulfonyl‑5,8‑dimethoxy‑1,4‑naphthoquinone 
      (ENDMNQ) were synthesized and their anti‑tumor activities were investigated. The 
      effects of EPDMNQ and ENDMNQ on cell viability, apoptosis and accumulation of 
      reactive oxygen species (ROS) in liver cancer cells were determined by MTT cell 
      viability assay and flow cytometry. The expression levels of mitochondrial, 
      mitogen activated protein kinase (MAPK) and signal transducer and activator of 
      transcription 3 (STAT3) signaling pathway‑associated proteins in Hep3B liver 
      cancer cells were analyzed by western blot analysis. The results demonstrated 
      that EPDMNQ and ENDMNQ inhibited the proliferation of liver cancer Hep3B, HepG2, 
      and Huh7 cell lines but not that of normal liver L‑02, normal lung IMR‑90 and 
      stomach GES‑1 cell lines. The number of apoptotic cells and ROS levels were 
      significantly increased following treatment with EPDMNQ and ENDMNQ, and these 
      effects were blocked by the ROS inhibitor N‑acetyl‑L‑cysteine (NAC) in Hep3B 
      cells. EPDMNQ and ENDMNQ induced apoptosis by upregulating the protein expression 
      of p38 MAPK and c‑Jun N‑terminal kinase and downregulating extracellular 
      signal‑regulated kinase and STAT3; these effects were inhibited by NAC. The 
      results of the present study demonstrated that EPDMNQ and ENDMNQ induced 
      apoptosis through ROS‑modulated MAPK and STAT3 signaling pathways in Hep3B cells. 
      Therefore, these novel 1,4‑naphthoquinone derivatives may be useful as anticancer 
      agents for the treatment of liver cancer.
FAU - Wang, Yue
AU  - Wang Y
AD  - Department of Biochemistry and Molecular Biology, College of Life Science and 
      Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 
      163319, P.R. China.
FAU - Luo, Ying-Hua
AU  - Luo YH
AD  - Department of Grass Science, College of Animal Science and Veterinary Medicine, 
      Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. 
      China.
FAU - Piao, Xian-Ji
AU  - Piao XJ
AD  - Department of Gynaecology and Obstetrics, The Fifth Affiliated Hospital of Harbin 
      Medical University, Daqing, Heilongjiang 163316, P.R. China.
FAU - Shen, Gui-Nan
AU  - Shen GN
AD  - Department of Biochemistry and Molecular Biology, College of Life Science and 
      Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 
      163319, P.R. China.
FAU - Meng, Ling-Qi
AU  - Meng LQ
AD  - Department of Biochemistry and Molecular Biology, College of Life Science and 
      Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 
      163319, P.R. China.
FAU - Zhang, Yi
AU  - Zhang Y
AD  - Department of Biochemistry and Molecular Biology, College of Life Science and 
      Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 
      163319, P.R. China.
FAU - Wang, Jia-Ru
AU  - Wang JR
AD  - Department of Biochemistry and Molecular Biology, College of Life Science and 
      Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 
      163319, P.R. China.
FAU - Li, Jin-Qian
AU  - Li JQ
AD  - Department of Biochemistry and Molecular Biology, College of Life Science and 
      Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 
      163319, P.R. China.
FAU - Wang, Hao
AU  - Wang H
AD  - Department of Biochemistry and Molecular Biology, College of Life Science and 
      Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 
      163319, P.R. China.
FAU - Xu, Wan-Ting
AU  - Xu WT
AD  - Department of Biochemistry and Molecular Biology, College of Life Science and 
      Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 
      163319, P.R. China.
FAU - Liu, Yang
AU  - Liu Y
AD  - Department of Biochemistry and Molecular Biology, College of Life Science and 
      Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 
      163319, P.R. China.
FAU - Zhang, Yu
AU  - Zhang Y
AD  - Department of Biochemistry and Molecular Biology, College of Life Science and 
      Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 
      163319, P.R. China.
FAU - Zhang, Tong
AU  - Zhang T
AD  - Department of Biochemistry and Molecular Biology, College of Life Science and 
      Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 
      163319, P.R. China.
FAU - Wang, Shi-Nong
AU  - Wang SN
AD  - Department of Biochemistry and Molecular Biology, College of Life Science and 
      Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 
      163319, P.R. China.
FAU - Sun, Hu-Nan
AU  - Sun HN
AD  - Department of Biochemistry and Molecular Biology, College of Life Science and 
      Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 
      163319, P.R. China.
FAU - Han, Ying-Hao
AU  - Han YH
AD  - Department of Biochemistry and Molecular Biology, College of Life Science and 
      Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 
      163319, P.R. China.
FAU - Jin, Mei-Hua
AU  - Jin MH
AD  - Department of Biochemistry and Molecular Biology, College of Life Science and 
      Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 
      163319, P.R. China.
FAU - Zang, Yan-Qing
AU  - Zang YQ
AD  - Department of Food Science and Engineering, College of Food Science, Heilongjiang 
      Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China.
FAU - Zhang, Dong-Jie
AU  - Zhang DJ
AD  - Department of Food Science and Engineering, College of Food Science, Heilongjiang 
      Bayi Agricultural University, Daqing, Heilongjiang 163319, P.R. China.
FAU - Jin, Cheng-Hao
AU  - Jin CH
AD  - Department of Biochemistry and Molecular Biology, College of Life Science and 
      Technology, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang 
      163319, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20181221
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Naphthoquinones)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - RBF5ZU7R7K (1,4-naphthoquinone)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Liver Neoplasms/*drug therapy/genetics/pathology
MH  - MAP Kinase Signaling System/drug effects
MH  - Mitochondria/drug effects/genetics
MH  - Naphthoquinones/*pharmacology
MH  - Reactive Oxygen Species/metabolism
MH  - STAT3 Transcription Factor/*genetics
MH  - p38 Mitogen-Activated Protein Kinases/*genetics
PMC - PMC6390020
EDAT- 2018/12/29 06:00
MHDA- 2019/05/28 06:00
PMCR- 2018/12/21
CRDT- 2018/12/29 06:00
PHST- 2018/03/29 00:00 [received]
PHST- 2018/11/15 00:00 [accepted]
PHST- 2018/12/29 06:00 [pubmed]
PHST- 2019/05/28 06:00 [medline]
PHST- 2018/12/29 06:00 [entrez]
PHST- 2018/12/21 00:00 [pmc-release]
AID - mmr-19-03-1654 [pii]
AID - 10.3892/mmr.2018.9785 [doi]
PST - ppublish
SO  - Mol Med Rep. 2019 Mar;19(3):1654-1664. doi: 10.3892/mmr.2018.9785. Epub 2018 Dec 
      21.