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Induction of Apoptosis by Coptisine in Hep3B Hepatocellular Carcinoma Cells through Activation of the ROS-Mediated JNK Signaling Pathway

Authors
  • Kim, So Young1, 2
  • Hwangbo, Hyun1, 2
  • Lee, Hyesook1, 3
  • Park, Cheol
  • Kim, Gi-Young
  • Moon, Sung-Kwon
  • Yun, Seok Joong4
  • Kim, Wun-Jae4
  • Cheong, Jaehun2
  • Choi, Yung Hyun1, 3
  • 1 (H.L.)
  • 2 Department of Molecular Biology, Pusan National University, Busan 46241, Korea
  • 3 Department of Biochemistry, Dong-Eui University College of Korean Medicine, Busan 47227, Korea
  • 4 (W.-J.K.)
Type
Published Article
Journal
International Journal of Molecular Sciences
Publisher
MDPI AG
Publication Date
Jul 31, 2020
Volume
21
Issue
15
Identifiers
DOI: 10.3390/ijms21155502
PMID: 32752099
PMCID: PMC7432186
Source
PubMed Central
Keywords
License
Green

Abstract

Hepatocellular carcinoma (HCC) has a high mortality rate worldwide, and treatment is very limited due to its high recurrence and low diagnosis rate, and therefore there is an increasing need to develop more effective drugs to treat HCC. Coptisine is one of the isoquinoline alkaloids, and it has various pharmacological effects. However, the evidence for the molecular mechanism of the anticancer efficacy is still insufficient. Therefore, this study investigated the antiproliferative effect of coptisine on human HCC Hep3B cells and identified the action mechanism. Our results showed that coptisine markedly increased DNA damage and apoptotic cell death, which was associated with induction of death receptor proteins. Coptisine also significantly upregulated expression of proapoptotic Bax protein, downregulated expression of anti-apoptotic Bcl-2 protein, and activated caspase-3, -8, and -9. In addition, coptisine remarkably increased the generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential (MMP), and release of cytochrome c into the cytoplasm. However, N -acetylcysteine (NAC), a ROS scavenger, significantly attenuated the apoptosis-inducing effect of coptisine. It is worth noting that coptisine significantly upregulated phosphorylation of ROS-dependent c-Jun N-terminal kinase (JNK), whereas treatment with JNK inhibitor could suppress an apoptosis-related series event. Taken together, our results suggest that coptisine has an anticancer effect in Hep3B cells through ROS-mediated activation of the JNK signaling pathway.

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