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01-08-2012 | PRECLINICAL STUDIES

Synergistic effects of the combination of β-ionone and sorafenib on metastasis of human hepatoma SK-Hep-1 cells

Authors: Chin-Shiu Huang, Shih-Chieh Lyu, Miao-Lin Hu

Published in: Investigational New Drugs | Issue 4/2012

Summary

The combination of anti-cancer drugs with nutritional factors is a potential strategy for improving the efficacy of chemotherapy, particularly for hepatocellular carcinoma because its conventional therapies are mostly ineffective. Using a highly invasive hepatoma SK-Hep-1 cell line, we investigated the possible synergistic anti-metastatic efficacy of a combination of sorafenib (SF), a multi-kinase inhibitor, and β-ionone (BI), a precursor of carotenoids. We found that SF (1 μM) in combination with BI (1 μM) synergistically inhibited cell invasion and additively inhibited cell migration, especially at 48 h of incubation. Mechanistically, the combination of SF and BI was found to decrease the protein expression of focal adhesion kinase (FAK) and Rho, and to enhance the protein expression of tissue inhibitor matrix metalloproteinase (TIMP)-1 and TIMP-2. In addition, the combination of SF and BI inhibited the activity of matrix metalloproteinase (MMP)-2 and MMP-9 and decreased the phosphorylation of FAK and of Rac1 proteins. Importantly, SF enhanced the suppressing effect of BI (1–50 μM) on the viability of SK-Hep-1 cells, but not on murine hepatic BNL CL.2 cells, indicating the selective cytotoxicity of this combination on tumor cells. The combination of SF and BI could be a potential therapeutic strategy against human hepatoma cells.

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Title: Synergistic effects of the combination of β-ionone and sorafenib on metastasis of human hepatoma SK-Hep-1 cells
Authors: Chin-Shiu Huang
Shih-Chieh Lyu
Miao-Lin Hu
Publication date: 01-08-2012
Publisher: Springer US
Published in: Investigational New Drugs / Issue 4/2012
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-011-9727-0

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