Cargando…

Novel 1,4-naphthoquinone derivatives induce reactive oxygen species-mediated apoptosis in liver cancer cells

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Yue, Luo, Ying-Hua, Piao, Xian-Ji, Shen, Gui-Nan, Meng, Ling-Qi, Zhang, Yi, Wang, Jia-Ru, Li, Jin-Qian, Wang, Hao, Xu, Wan-Ting, Liu, Yang, Zhang, Yu, Zhang, Tong, Wang, Shi-Nong, Sun, Hu-Nan, Han, Ying-Hao, Jin, Mei-Hua, Zang, Yan-Qing, Zhang, Dong-Jie, Jin, Cheng-Hao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390020/
https://www.ncbi.nlm.nih.gov/pubmed/30592276
http://dx.doi.org/10.3892/mmr.2018.9785
_version_ 1783398054254084096
author Wang, Yue
Luo, Ying-Hua
Piao, Xian-Ji
Shen, Gui-Nan
Meng, Ling-Qi
Zhang, Yi
Wang, Jia-Ru
Li, Jin-Qian
Wang, Hao
Xu, Wan-Ting
Liu, Yang
Zhang, Yu
Zhang, Tong
Wang, Shi-Nong
Sun, Hu-Nan
Han, Ying-Hao
Jin, Mei-Hua
Zang, Yan-Qing
Zhang, Dong-Jie
Jin, Cheng-Hao
author_facet Wang, Yue
Luo, Ying-Hua
Piao, Xian-Ji
Shen, Gui-Nan
Meng, Ling-Qi
Zhang, Yi
Wang, Jia-Ru
Li, Jin-Qian
Wang, Hao
Xu, Wan-Ting
Liu, Yang
Zhang, Yu
Zhang, Tong
Wang, Shi-Nong
Sun, Hu-Nan
Han, Ying-Hao
Jin, Mei-Hua
Zang, Yan-Qing
Zhang, Dong-Jie
Jin, Cheng-Hao
author_sort Wang, Yue
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6390020
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-63900202019-03-07 Novel 1,4-naphthoquinone derivatives induce reactive oxygen species-mediated apoptosis in liver cancer cells Wang, Yue Luo, Ying-Hua Piao, Xian-Ji Shen, Gui-Nan Meng, Ling-Qi Zhang, Yi Wang, Jia-Ru Li, Jin-Qian Wang, Hao Xu, Wan-Ting Liu, Yang Zhang, Yu Zhang, Tong Wang, Shi-Nong Sun, Hu-Nan Han, Ying-Hao Jin, Mei-Hua Zang, Yan-Qing Zhang, Dong-Jie Jin, Cheng-Hao Mol Med Rep Articles 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. D.A. Spandidos 2019-03 2018-12-21 /pmc/articles/PMC6390020/ /pubmed/30592276 http://dx.doi.org/10.3892/mmr.2018.9785 Text en Copyright: © Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Wang, Yue
Luo, Ying-Hua
Piao, Xian-Ji
Shen, Gui-Nan
Meng, Ling-Qi
Zhang, Yi
Wang, Jia-Ru
Li, Jin-Qian
Wang, Hao
Xu, Wan-Ting
Liu, Yang
Zhang, Yu
Zhang, Tong
Wang, Shi-Nong
Sun, Hu-Nan
Han, Ying-Hao
Jin, Mei-Hua
Zang, Yan-Qing
Zhang, Dong-Jie
Jin, Cheng-Hao
Novel 1,4-naphthoquinone derivatives induce reactive oxygen species-mediated apoptosis in liver cancer cells
title Novel 1,4-naphthoquinone derivatives induce reactive oxygen species-mediated apoptosis in liver cancer cells
title_full Novel 1,4-naphthoquinone derivatives induce reactive oxygen species-mediated apoptosis in liver cancer cells
title_fullStr Novel 1,4-naphthoquinone derivatives induce reactive oxygen species-mediated apoptosis in liver cancer cells
title_full_unstemmed Novel 1,4-naphthoquinone derivatives induce reactive oxygen species-mediated apoptosis in liver cancer cells
title_short Novel 1,4-naphthoquinone derivatives induce reactive oxygen species-mediated apoptosis in liver cancer cells
title_sort novel 1,4-naphthoquinone derivatives induce reactive oxygen species-mediated apoptosis in liver cancer cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390020/
https://www.ncbi.nlm.nih.gov/pubmed/30592276
http://dx.doi.org/10.3892/mmr.2018.9785
work_keys_str_mv AT wangyue novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells
AT luoyinghua novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells
AT piaoxianji novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells
AT shenguinan novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells
AT menglingqi novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells
AT zhangyi novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells
AT wangjiaru novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells
AT lijinqian novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells
AT wanghao novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells
AT xuwanting novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells
AT liuyang novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells
AT zhangyu novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells
AT zhangtong novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells
AT wangshinong novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells
AT sunhunan novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells
AT hanyinghao novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells
AT jinmeihua novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells
AT zangyanqing novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells
AT zhangdongjie novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells
AT jinchenghao novel14naphthoquinonederivativesinducereactiveoxygenspeciesmediatedapoptosisinlivercancercells