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Benzyl isothiocyanate inhibits basal and hepatocyte growth factor-stimulated migration of breast cancer cells

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Abstract

Benzyl isothiocyanate (BITC), which is found in cruciferous vegetables, has been shown to have anti-carcinogenic properties. Hepatocyte growth factor (HGF) has the ability to stimulate dissociation, migration, and invasion in various tumor cells, and abnormally increased expressions of HGF and its transmembrane tyrosine kinase receptor, c-Met, have previously been detected in human breast cancer, and are associated with high tumor grade and poor prognosis. In this study, in order to assess the mechanisms relevant to the BITC-induced regulation of breast cancer cell migration and invasion, MDA-MB-231 human breast cancer cells and 4T1 murine mammary carcinoma cells were cultured in the presence of 0–4 μmol/l BITC with or without 10 μg/l of HGF. BITC inhibited both the basal and HGF-induced migration of MDA-MB-231 and 4T1 cells in a dose-dependent manner. In MDA-MB-231 cells, BITC reduced both basal and HGF-induced secretion and activity of urokinase-type plasminogen activator (uPA). In addition, BITC increased the protein levels of plasminogen activator inhibitor-1. HGF stimulated c-Met and Akt phosphorylation, but did not affect the phosphorylation of extracellular signal-regulated kinase-1/2 or stress-activated protein/c-jun N-terminal kinase. BITC suppressed NF-κB activity and reduced the HGF-induced phosphorylation of c-Met and Akt in a dose-dependent manner. LY294002, a specific Akt inhibitor, reduced both basal and HGF-induced uPA secretion and migration of MDA-MB-231 cells. In this study, we demonstrated that BITC profoundly inhibits the migration and invasion of MDA-MB-231 cells, which is associated with reduced uPA activity, and also that these phenomena are accompanied by the suppression of Akt signaling.

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Acknowledgments

This study was supported by the Mid-career Researcher Program (2010-0006923) and a research grant from the National Research Foundation of Korea (NRF) for the Biofoods Research Program, Ministry of Education, Science, and Technology (MEST) and supported by the Ministry of Knowledge Economy through the Center for Efficacy Assessment and Development of Functional Foods and Drugs at Hallym University, Korea.

Conflict of interest

The authors have no conflicts of interests associated with this study to declare.

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Authors and Affiliations

  1. Department of Food Science and Nutrition, Hallym University, 39 Hallymdaehak-gil, Chuncheon, 200-702, Korea

    Jung Han Yoon Park

  2. Center for Efficacy Assessment and Development of Functional Foods and Drugs, Hallym University, 39 Hallymdaehak-gil, Chuncheon, 200-702, Korea

    Eun Ji Kim, Soon Ju Eom, Ji Eun Hong, Jae-Yong Lee & Jung Han Yoon Park

  3. Center for Food & Nutritional Genomics, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu, 702-701, Korea

    Myung-Sook Choi & Jung Han Yoon Park

  4. Department of Biochemistry, College of Medicine, Hallym University, 39 Hallymdaehak-gil, Chuncheon, 200-702, Korea

    Jae-Yong Lee

  5. Department of Food Science & Nutrition, 80 Daehak-ro, Buk-gu, Daegu, 702-701, Korea

    Myung-Sook Choi

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  1. Eun Ji Kim
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Correspondence to Jung Han Yoon Park.

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Kim, E.J., Eom, S.J., Hong, J.E. et al. Benzyl isothiocyanate inhibits basal and hepatocyte growth factor-stimulated migration of breast cancer cells. Mol Cell Biochem 359, 431–440 (2012). https://doi.org/10.1007/s11010-011-1039-3

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