SP-8356, a (1s)-(-)-verbenone derivative, inhibits the growth and motility of liver cancer cells by regulating NF-κB and ERK signaling

Dong Hwi Kim, Hyo Jeong Yong, Sunam Mander, Huong Thi Nguyen, Lan Phuong Nguyen, Hee Kyung Park, Hyo Kyeong Cha, Won Ki Kim, Jong Ik Hwang

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)331-341
Number of pages11
JournalBiomolecules and Therapeutics
Volume29
Issue number3
DOIs
Publication statusPublished - 2021

Keywords

  • ERK
  • Liver cancer
  • Motility
  • NF-κB
  • Proliferation
  • SP-8356

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

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