Sulforaphane,
a dietary component of broccoli/broccoli sprouts,
inhibits breast cancer stem cells
Source:
Department of Pharmaceutical Sciences, College
of Pharmacy, University of Michigan, Ann Arbor,
MI 48109, USA.
Abstract
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 beta-catenin
reporter assay.
RESULTS:
Sulforaphane (1-5 micromol/L) decreased aldehyde
dehydrogenase-positive cell population by
65% to 80% in human breast cancer cells (P
< 0.01) and reduced the size and number
of primary mammospheres by 8- to 125-fold
and 45% to 75% (P < 0.01), respectively.
Daily injection with 50 mg/kg sulforaphane
for 2 weeks reduced aldehyde dehydrogenase-positive
cells by >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 < 0.01).
Western blotting analysis and beta-catenin
reporter assay showed that sulforaphane downregulated
the Wnt/beta-catenin self-renewal pathway.
CONCLUSIONS:
Sulforaphane inhibits breast CSCs and downregulates
the Wnt/beta-catenin self-renewal pathway.
These findings support the use of sulforaphane
for the chemoprevention of breast cancer stem
cells and warrant further clinical evaluation.
Read
article at: http://www.ncbi.nlm.nih.gov
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