Breast Cancer Research and Treatment

, Volume 130, Issue 1, pp 61–71 | Cite as

Oral administration of benzyl-isothiocyanate inhibits solid tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice

  • Eun Ji Kim
  • Ji Eun Hong
  • Soon Ju Eom
  • Jae-Yong Lee
  • Jung Han Yoon Park
Preclinical study

Abstract

Benzyl-isothiocyanate (BITC) is a hydrolysis product of glucotropaeolin, a compound found in cruciferous vegetables, and has also been shown to have anti-tumor properties. To evaluate the effects of BITC administration on the tumor growth and metastasis of breast cancer, 4T1 murine mammary carcinoma cells were injected into the inguinal mammary fat pads of syngeneic female BALB/c mice. One day later, the mice were subjected to gavage for 4 weeks with BITC (0, 5, or 10 mg/kg body weight/day). Oral BITC treatment induced a significant reduction in the growth of solid tumors. BITC reduced hemoglobin contents and CD31 and vascular endothelial growth factor (VEGF) expression in the tumors, as well as circulating levels of VEGF. Reduced expressions of proliferating cell nuclear antigen and cyclin-dependent kinase 4 were noted in the tumors of BITC-treated mice. BITC markedly increased the numbers of apoptotic cells with increased Bax expression, cleaved caspase-3, and PARP levels, but reduced Bcl-2 expression in tumor tissues. In addition, BITC was shown to reduce the numbers of pulmonary tumor nodules and the total pulmonary metastatic volume. BITC induced a significant reduction in the levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and urokinase-type plasminogen activator in the sera and lungs of 4T1 cell-injected mice. However, the concentrations of TIMP-2 and plasminogen activator inhibitor-1 were increased in the sera and lungs of BITC-treated mice. The results of this study indicate that BITC has potential as a preventive agent for metastatic breast cancer.

Keywords

Benzyl-isothiocyanate Apoptosis Metastasis Cancer Angiogenesis 

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Eun Ji Kim
    • 2
  • Ji Eun Hong
    • 1
  • Soon Ju Eom
    • 2
  • Jae-Yong Lee
    • 2
    • 3
  • Jung Han Yoon Park
    • 1
    • 2
    • 4
  1. 1.Department of Food Science and NutritionHallym UniversityChuncheonKorea
  2. 2.Center for Efficacy Assessment and Development of Functional Foods and DrugsHallym UniversityChuncheonKorea
  3. 3.Department of Biochemistry, College of MedicineHallym UniversityChuncheonKorea
  4. 4.Medical and Bio-materials Research CenterHallym UniversityChuncheonKorea

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