Study2010

Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells

Li Y, Zhang T, Korkaya H, Liu S, Lee HF, Newman B, Yu Y, Clouthier SG, Schwartz SJ, Wicha MS, Sun D

Clinical cancer research : an official journal of the American Association for Cancer Research · 391 citations

Review labels

Mechanisms only

Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.

How it was studied

Design
In vitro/mechanistic study (classified by our AI screen)
Studied in
People, plus animal or lab work
Main outcome
Mechanisms only

Who paid for it

Funding
Independent funding
University or hospital
Barbara Ann Karmanos Cancer Institute
Government
National Institutes of Health
University or hospital
School of Medicine, Stanford University
University or hospital
Ludwig Center at Harvard
Government
National Cancer Institute
Government
National Center for Research Resources
Government
NCI NIH HHS
Government
NCRR NIH HHS
Grants
National Cancer Institute (P30CA016058); National Center for Research Resources (UL1 RR025755); National Cancer Institute (R01-CA120023)

Based on 8 listed funder(s).

Publication

Published
2010-04-14 · Clin Cancer Res · vol. 16 · issue 9 · pp. 2580–2590
Publisher
American Association for Cancer Research
Cited
569 citations · more than 100% of similar papers · 16.5× the field average
Impact
Top 10% most cited in its field
References
51 works
Access
Free to read
Research areas
Genomics, phytochemicals, and oxidative stress · Bioactive natural compounds · Curcumin's Biomedical Applications
Keywords
Sulforaphane, Cancer stem cell, Wnt signaling pathway, Cancer research, Breast cancer, Population, Aldehyde dehydrogenase, Stem cell, Chemistry, Cancer, Medicine, Pharmacology, Internal medicine, Biology, Biochemistry, Signal transduction, Cell biology, Enzyme
MeSH
cell line, tumor, spheroids, cellular, animals, mice, inbred nod, humans, mice, mice, scid, brassica, breast neoplasms, mammary neoplasms, experimental, thiocyanates, isothiocyanates, sulfoxides, isoenzymes, aldehyde dehydrogenase, anticarcinogenic agents, blotting, western, xenograft model antitumor assays, signal transduction, apoptosis, cell proliferation, dose-response relationship, drug, dietary supplements, female, retinal dehydrogenase, wnt proteins, beta catenin, neoplastic stem cells, seedlings, aldehyde dehydrogenase 1 family

11 authors

From US

  • Yanyan LiUniversity of Michigan; The Ohio State University
  • Tao ZhangUniversity of Michigan; The Ohio State University
  • Hasan KörkayaUniversity of Michigan; The Ohio State University
  • Suling LiuUniversity of Michigan; The Ohio State University
  • Hsiu-Fang LeeUniversity of Michigan; The Ohio State University
  • Bryan W. NewmanUniversity of Michigan; The Ohio State University

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 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.

Abstract via Europe PMC. Copyright remains with the authors or publisher.

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