Annals of Surgical Oncology

, Volume 16, Issue 2, pp 534–543 | Cite as

Sulforaphane Stimulates Activation of Proapoptotic Protein Bax Leading to Apoptosis of Endothelial Progenitor Cells

  • Takeshi Nishikawa
  • Nelson H. Tsuno
  • Takeshi Tsuchiya
  • Satomi Yoneyama
  • Jun Yamada
  • Yasutaka Shuno
  • Yurai Okaji
  • Junichiro Tanaka
  • Joji Kitayama
  • Koki Takahashi
  • Hirokazu Nagawa
Laboratory and Translational Research

Abstract

Sulforaphane (SUL) is an isothiocyanate naturally present in widely consumed vegetables, particularly in broccoli. SUL has recently been focused as a result of its inhibitory effects on tumor cell growth in vitro and in vivo. We used endothelial progenitor cells (EPCs) as an in vitro model to investigate the effect of SUL on the various steps of vasculogenesis and angiogenesis. Peripheral blood mononuclear cells from blood of normal human volunteers were plated on fibronectin-coated 100 mm dishes and incubated for 7 days. The viability of EPCs, treated with SUL at different doses, was assessed by MTS assay. Cell apoptosis was analyzed by flow cytometry. To determine the relative contributions of caspase-8 and caspase-9 pathways to SUL-induced apoptosis, the effect of caspase inhibitors was determined. The expression of apoptosis-related proteins (Bax, Bcl-2) was investigated by Western blot test. Finally, the effect of SUL on the ability of EPCs to form vascular-like structures on Matrigel was investigated. We clearly demonstrated that SUL induced the dose-dependent inhibition of EPCs’ viability by induction of apoptosis. All caspases (caspase-3, −8, and −9) were activated during apoptosis induction by SUL, but the effect of caspase-9 was more prominent than that of caspase-8. Also, the expression of Bax was upregulated by SUL treatment. In addition to apoptosis induction, SUL dose-dependently inhibited the tube-like formation by EPCs on Matrigel. The present results demonstrate the antivasculogenic/antiangiogenic activity of SUL in vitro and open premise for the use of SUL as a multipotent anticancer agent that targets both cancer cells and the angiogenic endothelium.

Keywords

Endothelial Progenitor Cell Sulforaphane Cruciferous Vegetable Phenazine Methosulfate Chloromethyl Ketone 

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Copyright information

© Society of Surgical Oncology 2008

Authors and Affiliations

  • Takeshi Nishikawa
    • 1
  • Nelson H. Tsuno
    • 1
    • 2
  • Takeshi Tsuchiya
    • 1
  • Satomi Yoneyama
    • 1
  • Jun Yamada
    • 1
  • Yasutaka Shuno
    • 1
  • Yurai Okaji
    • 2
  • Junichiro Tanaka
    • 1
  • Joji Kitayama
    • 1
  • Koki Takahashi
    • 2
  • Hirokazu Nagawa
    • 1
  1. 1.Department of Surgical OncologyUniversity of TokyoTokyoJapan
  2. 2.Faculty of Medicine, Department of Transfusion MedicineUniversity of TokyoTokyoJapan

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