Abstract

Abstract Sulforaphane, a Dietary Component of Broccoli/Broccoli Sprouts, Inhibits Breast Cancer Stem Cells The existence of cancer stem cells (CSCs) in breast cancer has profound implications for cancer prevention. The purpose of this study was to evaluate sulforaphane, a naturally occurring dietary compound from broccoli/broccoli sprouts, for its efficacy to inhibit breast CSCs as well as to elucidate the potential mechanisms of its effect. Aldefluor and mammosphere formation assays were used to assess the effect of sulforaphane on breast CSCs in vitro. A NOD/SCID xenograft model was employed to determine the efficacy of sulforaphane in targeting breast CSCs in vivo. The potential mechanism of sulforaphane was investigated utilizing Western blotting and β-catenin reporter assays. The results showed that sulforaphane (1∼5 µM) decreased aldehyde dehydrogenase (ALDH)-positive cell population by 65%∼80% in human breast cancer cell line (P < 0.01), and reduced the size and number of primary mammospheres by 8∼125-fold and 50%∼75% (P < 0.01), respectively. Daily injection with 50 mg/kg sulforaphane for two weeks reduced ALDH-positive cells by more than 50% in tumors (P = 0.003). Furthermore, sulforaphane eliminated breast CSCs in vivo, thereby abrogating tumor re-growth in secondary mice (P < 0.01). Western blotting showed that sulforaphane down-regulated the Wnt/β-catenin self-renewal pathway. These data suggest that sulforaphane targets breast CSCs through the down-regulation of the Wnt/β-catenin pathway as a potential mechanism. These findings provide a scientific rationale for use of sulforaphane and potentially broccoli/broccoli sprout dietary interventions for breast cancer chemoprevention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4271.

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