Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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SP-8356, a (1S)-(-)-Verbenone Derivative, Inhibits the Growth and Motility of Liver Cancer Cells by Regulating NF-κB and ERK Signaling

  • Kim, Dong Hwi (Department of Biomedical Science, Korea University College of Medicine) ;
  • Yong, Hyo Jeong (Department of Biomedical Science, Korea University College of Medicine) ;
  • Mander, Sunam (Department of Biomedical Science, Korea University College of Medicine) ;
  • Nguyen, Huong Thi (Department of Biomedical Science, Korea University College of Medicine) ;
  • Nguyen, Lan Phuong (Department of Biomedical Science, Korea University College of Medicine) ;
  • Park, Hee-Kyung (Department of Biomedical Science, Korea University College of Medicine) ;
  • Cha, Hyo Kyeong (Department of Biomedical Science, Korea University College of Medicine) ;
  • Kim, Won-Ki (Department of Biomedical Science, Korea University College of Medicine) ;
  • Hwang, Jong-Ik (Department of Biomedical Science, Korea University College of Medicine)
  • Received : 2020.11.05
  • Accepted : 2020.12.10
  • Published : 2021.05.01
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Abstract

Liver cancer is a common tumor and currently the second leading cause of cancer-related mortality globally. Liver cancer is highly related to inflammation as more than 90% of liver cancer arises in the context of hepatic inflammation, such as hepatitis B virus and hepatitis C virus infection. Despite significant improvements in the therapeutic modalities for liver cancer, patient prognosis is not satisfactory due to the limited efficacy of current drug therapies in anti-metastatic activity. Therefore, developing new effective anti-cancer agents with anti-metastatic activity is important for the treatment of liver cancer. In this study, SP-8356, a verbenone derivative with anti-inflammatory activity, was investigated for its effect on the growth and migration of liver cancer cells. Our findings demonstrated that SP-8356 inhibits the proliferation of liver cancer cells by inducing apoptosis and suppressing the mobility and invasion ability of liver cancer cells. Functional studies revealed that SP-8356 inhibits the mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways, which are related to cell proliferation and metastasis, resulting in the downregulation of metastasis-related genes. Moreover, using an orthotopic liver cancer model, tumor growth was significantly decreased following treatment with SP-8356. Thus, this study suggests that SP-8356 may be a potential agent for the treatment of liver cancer with multimodal regulation.

Keywords

References

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