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Cancer Prev Res (Phila). 2019 Jan 24. pii: canprevres.0241.2018. doi: 10.1158/1940-6207.CAPR-18-0241. [Epub ahead of print]

Sulforaphane suppresses the growth of triple-negative breast cancer stem-like cells in vitro and in vivo.

Author information

1
MCGP, National Institutes of Health.
2
Center for Cancer Research, National Institutes of Health.
3
NCI, National Institutes of Health.
4
Angiogenesis Core Facility, ROB, NCI, National Institute of Health.
5
Tumor Growth Factor Section, Mammary Biology and Tumorigenesis Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda.
6
NCI, National Institutes of Health kimyoung@mail.nih.gov.

Abstract

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 (SFN), a dietary component abundant in broccoli and its sprouts, can inhibit malignant cell proliferation and tumor sphere formation of cancer stem-like cells (CSCs) in TNBC. CSC population was isolated using fluorescently activated cell sorting (FACS) analysis with the combined stem cell surface markers, CD44+/CD24-/CD49f+. The effect of SFN on a stem-related embryonic oncogene CRIPTO-1/TDGF1 (CR1) was evaluated via enzyme-linked immunosorbent assay (ELISA). In vivo, BalbC/nude mice were supplemented with SFN before and after TNBC cell inoculation (daily i.p. injection of 50mg SFN/kg for 5 and 3 weeks respectively), and effects of SFN during mammary tumor initiation and growth were accessed with Nanostring gene analysis. We found that SFN can inhibit cell proliferation and mammosphere formation of CSCs in TNBC. Further analysis of gene expression in these TNBC tumor cells revealed that SFN 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 SFN 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 SFN for chemoprevention of TNBC is plausible and warrants further clinical evaluation.

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