Biomolecules & Therapeutics  https://doi.org/10.4062/biomolther.2020.200
SP-8356, a (1S)-(-)-Verbenone Derivative, Inhibits the Growth and Motility of Liver Cancer Cells by Regulating NF-κB and ERK Signaling
Dong Hwi Kim1,†, Hyo Jeong Yong1,†, Sunam Mander1, Huong Thi Nguyen1, Lan Phuong Nguyen1, Hee-Kyung Park1, Hyo Kyeong Cha1, Won-Ki Kim1,2,* and Jong-Ik Hwang1,*
1Department of Biomedical Science, Korea University College of Medicine, Seoul 02841,
2Department of Neuroscience, Korea University College of Medicine, Seoul 02841, Republic of Korea
*E-mail: hjibio@korea.ac.kr (Hwang JI), wonki@korea.ac.kr (Kim WK)
Tel: +82-2-2286-1093 (Hwang JI), +82-2-2286-6094 (Kim WK)
Fax: +82-2-921-4355 (Hwang JI), +82-2-953-6095 (Kim WK)
†The first two authors contributed equally to this work.
Received: November 5, 2020; Revised: December 7, 2020; Accepted: December 10, 2020; Published online: January 18, 2021.
© The Korean Society of Applied Pharmacology. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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: SP-8356, Liver cancer, Proliferation, Motility, ERK, NF-κB

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