Sulforaphane, a Dietary Component of Broccoli/Broccoli Sprouts, Inhibits Breast Cancer Stem Cells

Purpose: The existence of cancer stem cells (CSCs) in breast cancer has profound implications for cancer prevention. In this study, we evaluated sulforaphane, a natural compound derived from broccoli/broccoli sprouts, for its efficacy to inhibit breast CSCs and its potential mechanism. Experimental Design: Aldefluor assay and mammosphere formation assay were used to evaluate the effect of sulforaphane on breast CSCs in vitro . A nonobese diabetic/severe combined immunodeficient xenograft model was used to determine whether sulforaphane could target breast CSCs in vivo , as assessed by Aldefluor assay, and tumor growth upon cell reimplantation in secondary mice. The potential mechanism was investigated using Western blotting analysis and β-catenin reporter assay. Results: Sulforaphane (1-5 μmol/L) decreased aldehyde dehydrogenase–positive cell population by 65% to 80% in human breast cancer cells ( P P 50% in nonobese diabetic/severe combined immunodeficient xenograft tumors ( P = 0.003). Sulforaphane eliminated breast CSCs in vivo , thereby abrogating tumor growth after the reimplantation of primary tumor cells into the secondary mice ( P Conclusions: Sulforaphane inhibits breast CSCs and downregulates the Wnt/β-catenin self-renewal pathway. These findings support the use of sulforaphane for the chemoprevention of breast cancer stem cells and warrant further clinical evaluation. Clin Cancer Res; 16(9); 2580–90. ©2010 AACR.