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Novel 1,4‑naphthoquinone derivatives induce reactive oxygen species‑mediated apoptosis in liver cancer cells
- Source :
- Molecular Medicine Reports
- Publication Year :
- 2018
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
STAT3 Transcription Factor
Cancer Research
mitogen-activated protein kinase
Cell Survival
MAP Kinase Signaling System
Biochemistry
p38 Mitogen-Activated Protein Kinases
03 medical and health sciences
Cell Line, Tumor
Genetics
Humans
Viability assay
STAT3
Molecular Biology
Cell Proliferation
chemistry.chemical_classification
reactive oxygen species
Reactive oxygen species
biology
Chemistry
Kinase
Liver Neoplasms
apoptosis
Articles
Cell cycle
1,4-naphthoquinone derivatives
hepatocellular carcinoma cells
Mitochondria
Gene Expression Regulation, Neoplastic
030104 developmental biology
Oncology
Cell culture
Apoptosis
biology.protein
Cancer research
signal transducer and activator of transcription 3
Molecular Medicine
Naphthoquinones
Subjects
Details
- ISSN :
- 17913004
- Volume :
- 19
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Molecular medicine reports
- Accession number :
- edsair.doi.dedup.....d9777b63f92adb7076b36ac8cfb69d0b