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KMID : 0606920210290030331
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Biomolecules & Therapeutics
2021 Volume.29 No. 3 p.331 ~ p.341
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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
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Kim Dong-Hwi
Yong Hyo-Jeong
Mander Sunam
Nguyen Huong Thi
Nguyen Lan Phuong
Park Hee-Kyung
Cha Hyo-Kyeong
Kim Won-Ki
Hwang Jong-Ik
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Abstract
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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.
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KEYWORD
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SP-8356, Liver cancer, Proliferation, Motility, ERK, NF-κB
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