Triple-negative breast cancer (TNBC) represents the poorest prognosis among all of
breast cancer subtypes with no currently available effective
therapy. In this study, we hypothesized that
sulforaphane, a dietary component abundant in broccoli and its sprouts, can inhibit malignant cell proliferation and
tumor sphere formation of
cancer stem-like cells (CSC) in TNBC. CSC population was isolated using FACS analysis with the combined stem cell surface markers, CD44+/CD24-/CD49f+ The effect of
sulforaphane on a stem-related embryonic oncogene CRIPTO-1/TDGF1 (CR1) was evaluated via ELISA. In vivo, BalbC/nude mice were supplemented with
sulforaphane before and after TNBC cell inoculation (daily
intraperitoneal injection of 50 mg
sulforaphane/kg for 5 and 3 weeks, respectively), and the effects of
sulforaphane during mammary
tumor initiation and growth were accessed with NanoString gene analysis. We found that
sulforaphane can inhibit cell proliferation and mammosphere formation of CSCs in TNBC. Further analysis of gene expression in these TNBC
tumor cells revealed that
sulforaphane significantly decreases the expression of
cancer-specific CR1, CRIPTO-3/TDGF1P3 (CR3, a homologue of CR1), and various stem cell markers including Nanog,
aldehyde dehydrogenase 1A1 (ALDH1A1), Wnt3, and Notch4. Our results suggest that
sulforaphane may control the malignant proliferation of CSCs in TNBC via Cripto-mediated pathway by either suppressing its expression and/or by inhibiting Cripto/Alk4
protein complex formation. Thus, the use of
sulforaphane for
chemoprevention of TNBC is plausible and warrants further clinical evaluation.